International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis

The prevalence of food-induced rhinitis appears to be under 1%.

“The prevalence of “food-induced rhinitis” seems to be under 1%.157”

• cites [157] sourceDisputed

  The Discussion calls gustatory rhinitis a common phenomenon affecting a large portion of the population, contrary to a prevalence under 1%. The Food questionnaire section reports that hot chili peppers caused rhinorrhea in more than 60% of its 60 respondents; this is not a population-wide prevalence estimate, but it further contradicts the claimed figure. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

In 28 individuals with SAR history, 11% in both the group with negative SPT but positive intradermal Timothy and the group with negative SPT and negative intradermal had positive nasal challenge with Timothy grass.

“In both groups, 11% of individuals had a positive nasal challenge with Timothy grass.”

• cites [856] sourceDisputed

  The Nasal challenge section reports positive challenge results in 44% of group I and 42% of group III, not 11% in each. Table II gives 11% for each group only after a further assessment classified which challenge reactions indicated allergy; the citing sentence conflates that classification with a positive nasal challenge. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Modern SPT of aeroallergens can be up to 25% more sensitive than specific IgE serology depending on the patient population and methodologies employed.

“Modern SPT of aeroallergens can be up to 25% more sensitive than sIgE serology depending on the patient population and the methodologies employed.793,930-934”

• cites [793] sourceNot checked — no full text of the source
• cites [930] sourceNot checked — no full text of the source
• cites [931] sourceDisputed

  The Results and Discussion (pages not available) report the opposite comparison in the children studied: SPT alone would have missed an average of 42% of sensitizations, versus 13% with sIgE serology alone. The paper finds discordance between the tests, but does not report SPT as up to 25% more sensitive. (LLM, conf=0.85)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [932] sourceNot checked — no full text of the source
• cites [933] sourcePartly supported

  The Environmental and occupational disorders section says latex skin prick testing was more sensitive than serum-specific IgE assays for detecting natural rubber latex allergy in health care workers. The Study design section mentions aeroallergen skin tests, but the serum IgE tests measured latex; the paper does not establish the claimed comparison for aeroallergens or the ‘up to 25%’ figure. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [934] sourceNot checked — no full text of the source

In the OMIT versus SLIT pilot study, no adverse events were reported.

“No adverse events were reported, and there were no significant differences between outcome measures for both treatment arms.1729”

• cites [1729] sourceDisputed

  The Results section (AEs; page not provided) reports 11 adverse events in each treatment group, contrary to the claim that none were reported. The abstract says no *severe* adverse events occurred, which is a narrower finding. (LLM, conf=0.95)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Despite improvement in asthma symptoms, oral H1 antihistamines have failed to show significant improvements in objective pulmonary function testing and peak expiratory flow.

“Despite improvement in asthma symptoms, objective measures using pulmonary function testing and peak expiratory flow have failed to demonstrate significant improvements.1804-1806”

• cites [1804] sourceNot checked — no full text of the source
• cites [1805]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [1806] sourceDisputed

  The Results report statistically significant, though small, improvements in both morning and evening peak expiratory flow, contrary to the claim that peak expiratory flow failed to improve significantly. The FEV1 result was not statistically significant, and the Discussion says symptom scores could not be combined in the meta-analysis. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

A large population-based survey of allergic rhinitis patients demonstrated a strong correlation between allergic rhinitis disease severity and sleep disturbance.

“A large population-based survey of AR patients demonstrated a strong correlation between AR disease severity and sleep disturbance.679”

• cites [679] sourceDisputed

  The Patient population section describes 63 carefully selected patients randomly allocated to vaccine or placebo, not a large population-based survey. Table III in the Discussion compares sleep-domain scores between treatment groups; it does not report a correlation between allergic rhinitis severity and sleep disturbance. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Preventing and identifying occupational rhinitis early during medical surveillance of exposed workers and young apprentices may provide an opportunity to prevent occupational asthma.

“The prevention and early identification of occupational rhinitis during medical surveillance of exposed workers and of young apprentices may provide an excellent opportunity to prevent the development of occupational asthma.110,111”

• cites [110] sourceSupported
• cites [111] sourceNot checked — no full text of the source

Neurogenic nasal inflammation is mediated by neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide, which are released by sensory nerve fibers in the nose and cause vasodilation, edema, and inflammation.

“Neurogenic nasal inflammation is mediated by neuropeptides such as substance P, neurokinin A, and calcitonin gene-related peptide. These mediators are released by sensory nerve fibers in the nose and result in vasodilation, edema, and inflammation.133”

• cites [133] sourceSupported

Chemicals known to cause respiratory tract sensitization include diisocyanates, acid anhydrides, some platinum salts, reactive dyes, glutaraldehyde, plicatic acid, and chroamine.

“Chemicals known to cause sensitization of the respiratory tract include diisocyanates, acid anhydrides, some platinum salts, reactive dyes, glutaraldehyde, plicatic acid, and chroamine.118-120”

• cites [118] sourceNot checked — no full text of the source
• cites [119] sourceNot checked — no full text of the source
• cites [120] sourcePartly supported

  The Results tables list diisocyanates, several anhydrides, platinum salts, reactive dyes, glutaraldehyde, and chloramine T as occupational-asthma agents or inhalation sensitizers. Our copy does not identify plicatic acid or an agent named “chroamine”; the latter may be a misspelling of chloramine, but the paper does not establish that equivalence. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Pharmacologic treatment of allergic occupational rhinitis does not differ from treatment of non-occupational rhinitis.

“Pharmacologic treatment does not differ from that of non-occupational rhinitis.101”

• cites [101] sourceCould not verify

  Section 2.3.2 describes occupational rhinitis, and the Pharmacotherapy section discusses treatment of allergic rhinitis generally. Neither passage compares pharmacologic treatment for occupational and non-occupational rhinitis; searches for that comparison found no such statement in the available copy. (LLM, conf=0.68)

  Experimental — accuracy not yet measured

Approximately 2% of viral rhinitis episodes are secondarily infected by bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with subsequent acute bacterial infection.

“Approximately 2% of viral rhinitis episodes are secondarily infected by bacterial organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, with subsequent presentation of acute bacterial infection.138”

• cites [138] sourcePartly supported

  Section 2.2, “Clinical definition of rhinosinusitis in children” (page unavailable), says that a small percentage of patients with post-viral acute rhinosinusitis develop bacterial acute rhinosinusitis. It does not give a 2% rate for viral rhinitis episodes or name the three bacterial species; it also uses post-viral rhinosinusitis patients, rather than all viral rhinitis episodes, as the denominator. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Nasal biopsies from NARES patients commonly show increased numbers of mast cells and prominent mast cell degranulation.

“In addition, nasal biopsies from these patients commonly show increased numbers of mast cells and prominent mast cell degranulation.177,178”

• cites [177] sourcePartly supported

  The Mast cells results and Mast cells and IgE+ cells discussion report increased epithelial mast cells in idiopathic rhinitis compared with controls, with most of those cells degranulated. However, the paper studied patients selected for idiopathic rhinitis, not specifically NARES; its Eosinophils discussion says not all idiopathic cases had increased eosinophils. The findings therefore support the mast-cell observations but not their attribution specifically to NARES patients. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [178] sourceNot checked — no full text of the source

Gustatory rhinitis is considered a reflex response due to an adrenergic and cholinergic neural reaction of the nose.

“This is considered a reflex response due to an adrenergic and cholinergic neural reaction of the nose.157”

• cites [157] sourcePartly supported

  The Discussion (page not available) proposes a neural reflex involving atropine-inhibitable parasympathetic nerves supplying the nasal mucosa and glands, supporting the reflex and cholinergic parts of the claim. It does not identify an adrenergic nasal reaction, so that added mechanism is unsupported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

In gustatory rhinitis, shortly after ingestion of hot or spicy foods, unilateral or bilateral watery rhinorrhea develops without nasal congestion, pruritus, or facial pain.

“For instance, in subjects with gustatory rhinitis, shortly after ingestion of hot or spicy foods, unilateral or bilateral watery rhinorrhea develops in the absence of nasal congestion, pruritus, or facial pain.”

• cites [157] sourcePartly supported

  The Discussion says watery rhinorrhea begins within minutes of eating hot or spicy foods and that subjects do not complain of congestion or pruritus. Nasal and food challenges reports bilateral rhinorrhea in all challenged subjects, but the copy does not establish unilateral rhinorrhea or address facial pain. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

The absence of an IgE-mediated immune response differentiates vasomotor from allergic forms of rhinitis.

“The absence of an IgE-mediated immune response differentiates vasomotor from allergic forms of rhinitis.101”

• cites [101] sourcePartly supported

  The Introduction (§2.1; page unavailable) associates allergic rhinitis with an IgE-mediated response. The paper places idiopathic rhinitis, sometimes called “vasomotor rhinitis,” among nonallergic conditions, but does not explicitly establish absence of IgE as its distinguishing criterion. It also cautions that vasomotor symptoms can occur in both allergic and nonallergic rhinitis. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Nasal dryness and intranasal crusting in the elderly are likely due to age-related changes of the nasal mucosa, such as decreased mucosal blood flow and increased epithelial atrophy.

“This is likely due to age-related changes of the nasal mucosa,199 such as a decrease in mucosal blood flow and an increase in epithelial atrophy.213”

• cites [199] sourceNot checked — no full text of the source
• cites [213] sourceSupported

Nasal dryness in the elderly may also be caused by a decrease in intranasal temperature and humidity.

“Nasal dryness in the elderly population may also be caused by a decrease in intranasal temperature and humidity.200”

• cites [200] sourceSupported

The elderly population is more vulnerable to symptoms such as rhinorrhea, nasal congestion, postnasal drip, dry nose, intranasal crusting, and decreased olfaction.

“This makes the elderly population more vulnerable to symptoms such as rhinorrhea, nasal congestion, postnasal drip, dry nose, intranasal crusting, and decreased olfaction.199,200”

• cites [199] sourceNot checked — no full text of the source
• cites [200] sourceSupported

Recent research has validated that the primary physiological mechanism producing the sensation of ample nasal airflow is activation of trigeminal cool thermoreceptors, specifically TRPM8, by nasal mucosal cooling.

“Recent research has validated that the primary physiological mechanism that produces the sensation of ample nasal airflow is activation of trigeminal cool thermoreceptors, specifically TRPM8, by nasal mucosal cooling.224-228”

• cites [224] sourcePartly supported

  The Abstract and Conclusions identify nasal mucosal heat loss and trigeminal sensory input as important to perceived patency. But the Introduction describes TRPM8's role in nasal patency as possible, and the Discussion says TRPM8-targeting agents were not used in this pilot study. The paper therefore does not validate TRPM8 activation specifically as the primary mechanism. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [225] sourcePartly supported

  The Discussion (page unavailable) reports that regional peak mucosal heat loss significantly contributes to perceived nasal patency. The Introduction and Discussion link cool trigeminal afferents and TRPM8 to cooling, but this study does not establish TRPM8 activation as the primary mechanism producing the sensation of ample airflow. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [226] sourceNot checked — no full text of the source
• cites [227] sourcePartly supported

  The Discussion (page not provided) says mucosal cooling is sensed by nasal thermoreceptors and contributes to perceived nasal patency. It does not identify those receptors as trigeminal or TRPM8, and it calls for future research on the relative contributions of cooling and other variables rather than establishing cooling as the primary mechanism. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [228] sourceNot checked — no full text of the source

EGPA diagnosis should be suspected in patients with asthma, increased peripheral blood eosinophil count (>10%), and pulmonary manifestations.

“Diagnosis should be suspected in patients with asthma, with increased peripheral blood eosinophil count (>10%) and pulmonary manifestations.238,248”

• cites [238] sourceNot checked — no full text of the source
• cites [248] sourcePartly supported

  Section 3 (recommendation 2; page not supplied) links asthma, eosinophilia and pulmonary infiltrates to EGPA evaluation. It does not give a >10% peripheral-blood eosinophil threshold, and its description of a straightforward diagnosis also includes sinus disease and evidence of vasculitis. The cited paper therefore supports suspicion in this clinical context, but not the claim's precise threshold. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

AR shares overlapping symptoms of rhinorrhea and nasal congestion with rhinosinusitis subtypes.

“AR shares several overlapping symptoms, namely rhinorrhea and nasal congestion, which may be confused with the subtypes of rhinosinusitis.264,265”

• cites [264] sourcePartly supported

  The Introduction and Diagnosis of AR sections identify watery rhinorrhea and nasal obstruction as AR symptoms. The Rhinosinusitis section discusses acute and chronic rhinosinusitis and mentions nasal obstruction in patients with both AR and acute rhinosinusitis, but it does not establish that both symptoms overlap with rhinosinusitis subtypes or that the conditions may be confused. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [265] sourceNot checked — no full text of the source

EGPA treatment usually includes high doses of corticosteroids and immunosuppressants.

“Treatment usually includes high doses of corticosteroids and immunosuppressants.248,251”

• cites [248] sourcePartly supported

  The treatment recommendations (p. 548) call for high-dose glucocorticoids during induction and an additional immunosuppressant for life- or organ-threatening EGPA. Recommendation 12 says glucocorticoids alone may be suitable without those manifestations, so the claim overgeneralizes the use of both drugs as usual treatment. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [251] sourceNot checked — no full text of the source

A longer duration of illness suggests bacterial ARS.

“A longer duration of illness suggests bacterial ARS.137,138”

• cites [137] sourceSupported
• cites [138] sourceCould not verify

  Section 2.2 distinguishes post-viral from bacterial acute rhinosinusitis and says only a small percentage of post-viral cases are bacterial. It does not say whether a longer illness makes bacterial ARS more likely; searches for illness duration and persistent symptoms found no passage addressing that link. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Viral ARS is generally present for less than 10 days.

“In general, viral ARS is present for less than 10 days.”

• cites [137] sourceSupported
• cites [138] sourceCould not verify

  Section 2.2 identifies viral ARS with the common cold but gives no duration. Searches for “10 days,” “less than 10 days,” and the viral-versus-post-viral distinction found no passage in our copy establishing the claimed time limit. (LLM, conf=0.69)

  Experimental — accuracy not yet measured

Development of acute, moderate to severe symptoms and nasal purulence may be consistent with ARS or RARS rather than AR.

“The development of acute, moderate to severe symptoms, and nasal purulence may be consistent with ARS or RARS rather than AR.1,137,138”

• cites [1] sourceNot checked — no full text of the source
• cites [137] sourcePartly supported

  The guideline defines ARS by acute purulent nasal drainage accompanied by nasal obstruction or facial pain-pressure-fullness (Cardinal Symptoms of Acute Rhinosinusitis, p. 6). It defines RARS by four or more qualifying bacterial episodes per year (Recurrent Acute Rhinosinusitis, p. 21), so one episode of acute symptoms does not establish RARS. The cited passages do not establish moderate-to-severe symptoms as a distinguishing feature or directly compare this presentation with allergic rhinitis. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [138] sourcePartly supported

  Sections 2.1 and 2.2 include nasal discharge and mucopurulent discharge in the clinical definition of rhinosinusitis, and section 2.2 discusses acute rhinosinusitis. The retrieved passages do not establish that moderate-to-severe symptoms or nasal purulence distinguish ARS or RARS from allergic rhinitis, and they do not address RARS specifically. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

AR is typically not associated with purulent or unilateral nasal discharge.

“Conversely, AR is typically not associated with purulent or unilateral nasal discharge.”

• cites [1] sourceNot checked — no full text of the source
• cites [137] sourceCould not verify

  The Definition (p. 9) describes purulent discharge in acute rhinosinusitis, while Testing for Allergy (p. 26) discusses allergic rhinitis’s association with sinusitis. Neither passage characterizes discharge in allergic rhinitis as typically nonpurulent or nonunilateral. Searches for allergic-rhinitis symptoms and unilateral discharge found no passage addressing that claim. (LLM, conf=0.72)

  Experimental — accuracy not yet measured
• cites [138] sourceCould not verify

  The clinical definitions of rhinosinusitis (sections 2.1–2.2; page unavailable) list mucopurulent discharge as a possible sign of rhinosinusitis, but do not describe the usual discharge in allergic rhinitis. Searches for unilateral discharge and for a comparison with allergic rhinitis found no passage establishing that purulent or unilateral discharge is typically absent in allergic rhinitis. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

Progressive worsening over a short period (5 days) suggests bacterial ARS.

“Progressive worsening over a short period of time (ie, 5 days) is also suggestive of bacterial ARS.137,138”

• cites [137] sourcePartly supported

  The guideline’s “Transition from Viral to Bacterial Infection” section (p. 9) says that, between days 5 and 10, initial improvement followed by worsening (“double worsening”) is consistent with bacterial ARS. It does not say that progressive worsening over 5 days, without initial improvement, is suggestive of bacterial ARS. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [138] sourceCould not verify

  Section 2.2 distinguishes post-viral from bacterial acute rhinosinusitis but does not say that worsening over five days suggests a bacterial cause. Searches for “5 days,” worsening symptoms, and bacterial diagnostic criteria found no passage addressing that indicator in our copy. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

Fever is not included in other ARS guidelines due to its low specificity and sensitivity.

“Fever is not included in other guidelines, due to its low specificity and sensitivity.137”

• cites [137] sourcePartly supported

  In “Transition from Viral to Bacterial Infection” (p. 10), the guideline says fever has about 50% sensitivity and specificity for ABRS and explains that it therefore did not include fever as a cardinal diagnostic sign. The same section says other guidelines do use high fever in criteria for severe presentations, so this source does not support the broader claim that fever is omitted from other guidelines generally. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

AR symptoms are exacerbated by allergen exposure in a time-dependent fashion.

“AR symptoms are also exacerbated by exposure to allergens in a time dependent fashion.264”

• cites [264] sourceSupported

Several in vivo and in vitro studies have confirmed production of local IgE in the nasal mucosa of AR patients.

“Several studies, both in vivo and in vitro have confirmed the production of local IgE in the nasal mucosa of patients with AR.282-284”

• cites [282] sourceNot checked — no full text of the source
• cites [283] sourceNot checked — no full text of the source
• cites [284] sourcePartly supported

  The Discussion (page unavailable) describes nasal B cells locally producing IgE and reports mucosal allergen binding in allergic rhinitis subjects; the References also identify studies of local IgE production. Our copy does not establish the claim’s distinction that both in vivo and in vitro studies confirmed this finding. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Locally produced IgE plays a key role in ongoing inflammation by up-regulating FcεRI expression in mast cells.

“The locally produced IgE plays a key role in ongoing inflammation by up-regulating FcεRI expression in mast cells.283-285”

• cites [283] sourceNot checked — no full text of the source
• cites [284] sourcePartly supported

  The Discussion (page unavailable) links localized nasal IgE production with mucosal allergic inflammation and reports allergen co-localization with mast cells. It does not say that locally produced IgE sustains inflammation by up-regulating FcεRI expression in mast cells; the paper instead suggests that inflammatory cells may help maintain IgE production. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [285]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Whether AR develops after inhalant allergen exposure depends largely on the balance between Th1 and Th2 effector cells.

“Whether AR will develop as a result of inhalant allergen exposure therefore depends largely upon the balance between Th1 and Th2 effector cells.274”

• cites [274] sourcePartly supported

  The Introduction says Th2 cells support allergic responses and describes atopic disease as an overly aggressive Th2 response to environmental antigens. It does not specifically say that allergic rhinitis after inhalant exposure depends largely on the Th1–Th2 balance; it cautions that atopic disorders do not simply reflect over-polarization of the T-cell response. No page number is available in our copy. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

GATA-3 activation stimulates production of IL-4, IL-5, and IL-13, characteristic of the Th2 response.

“This stimulates IL-4, IL-5, and IL-13 production,274 which is characteristic of the Th2 response.”

• cites [274] sourcePartly supported

  The Introduction says Th2 cells express GATA-3 and produce IL-4, IL-5, and IL-13, supporting the cytokine profile attributed to a Th2 response. It does not say that activation of GATA-3 stimulates their production, so the causal part of the claim is not established by this copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Th2 differentiation requires co-stimulation via interaction of CD28 on T cells with CD80 and CD86 on antigen-presenting cells.

“Th2 differentiation also requires co-stimulation via the interaction of CD28 on T cells with CD80 and CD86 on antigen-presenting cells (APCs).278”

• cites [278] sourcePartly supported

  The Introduction and §1.5 identify CD28 as a T-cell costimulatory receptor and B7.1/B7.2 (CD80/CD86) as its ligands. They do not establish that this interaction is required specifically for Th2 differentiation; §1.5 notes that mice lacking CD28 or both ligands still produced reduced levels of effector cytokines. Page numbers are unavailable in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Epithelial cells provide an early stimulus toward a Th2-weighted immune response through secretion of TSLP.

“They also provide an important early stimulus toward a Th2-weighted immune response, through the secretion of thymic stromal lymphopoietin (TSLP).272,275,276”

• cites [272] sourceNot checked — no full text of the source
• cites [275] sourceNot checked — no full text of the source
• cites [276] sourceSupported

Innate lymphoid cells (ILCs) have been discovered as potential key players in pathogenesis of Th2-type diseases such as AR, CRSwNP, and asthma.

“An interesting recent development was the discovery of innate lymphoid cells (ILCs) as potential key players in the pathogenesis of Th2-type diseases such as AR, CRSwNP, and asthma.328-330”

• cites [328] sourceNot checked — no full text of the source
• cites [329] sourceSupported
• cites [330] sourcePartly supported

  The Introduction reports increased ILC2s in allergic asthma and their accumulation in nasal polyps and sinus mucosa in chronic rhinosinusitis, supporting a potential role in asthma and CRSwNP. It also says increased innate type 2 responses were not observed in allergic rhinitis (AR). The Discussion suggests ILC2s may play a more prominent role in asthma than in AR, so the source does not support treating all three diseases alike. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Flow cytometry studies in nasal secretions have confirmed that aeroallergen exposure induces a Th2 inflammatory response in the nasal mucosa of LAR patients with increased eosinophils, basophils, mast cells, CD3+, and CD4+ T cells.

“Flow cytometry studies in nasal secretions have confirmed that aeroallergen exposure induces a Th2 inflammatory response in the nasal mucosa of LAR patients with increased eosinophils, basophils, mast cells, CD3+, and CD4+ T cells.300,301”

• cites [300] sourcePartly supported

  The Discussion (page unavailable) reports flow-cytometry evidence of increased nasal eosinophils, basophil–mast cells and CD3+ T cells in patients with seasonal idiopathic rhinitis who responded to pollen challenge. It does not report a significant increase in CD4+ T cells; the Results passage says no differences were found in the other measured values. The paper describes inflammation during seasonal pollen exposure, but does not establish that exposure induced a specifically Th2 response. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [301] sourceNot checked — no full text of the source

Understanding of the contributions of the nasal innate immune response to AR pathogenesis has grown substantially in recent years.

“However, in recent years our understanding and appreciation of the important contributions of the nasal innate immune response to the pathogenesis of AR has grown substantially.320”

• cites [320] sourceSupported

In LAR, presence of sIgE in nasal secretions has been confirmed after natural allergen exposure, NPT, and periods of non-exposure.

“In LAR, the presence of sIgE in nasal secretions has been confirmed after natural allergen exposure,300,301 NPT,300,301,303-305 and periods of non-exposure.300,301”

• cites [300] sourcePartly supported

  The Natural exposure to pollen (April–June) methods and Symptom score results report nasal sIgE in 7 of 32 patients with seasonal idiopathic rhinitis during pollen exposure. The Determinations made outside the pollen season section reports positive NAPT responses and says all patients with nasal sIgE had a positive NAPT. It does not report detecting sIgE in nasal secretions after NAPT or during non-exposure. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [301] sourceNot checked — no full text of the source

Intrinsic proteolytic activity of allergens may disrupt the nasal epithelial barrier, facilitating allergen penetration and chronic inflammation.

“Intrinsic proteolytic activity of allergens may disrupt the nasal epithelial barrier, facilitating allergen penetration and chronic inflammation.321”

• cites [321] sourcePartly supported

  The Results (page unavailable) show that Bermuda grass pollen cysteine protease increased permeability of human airway epithelial cells; the paper also describes protease-bearing allergens facilitating allergen access. It did not test barrier disruption specifically in nasal epithelial cells or establish that this process leads to chronic inflammation, although it reports inflammatory responses and nasal eosinophil influx in mice. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

The systemic allergic response is characterized by increased expression of adhesion molecules VCAM-1 and E-selectin on nasal and bronchial endothelium, facilitating migration of inflammatory cells into tissue.

“The systemic allergic response is further characterized by increased expression of adhesion molecules, such as vascular cell adhesion molecule 1 and E-selectin on nasal and bronchial endothelium, which facilitates the migration of inflammatory cells into the tissue.352”

• cites [352] sourceSupported

Newer evidence identifies B-cells and plasma cells capable of producing IgE in nasal tissue of AR patients.

“Although it was believed that IgE-producing B-cells reside in lymphoid follicles of the Waldeyer ring376 and antibodies were then transferred to the mucosa, newer evidence has identified B-cells and plasma cells capable of producing IgE in nasal tissue of AR patients.377”

• cites [377] sourceSupported

Epithelial barrier leakiness, particularly of tight junctions sealing the upper and lower respiratory mucosal epithelial surface, has been shown in asthma, AR, and CRS.

“Epithelial barrier leakiness, particularly tight junctions that seal the upper and lower respiratory mucosal epithelial surface, has been shown in asthma, AR and CRS.343,344”

• cites [343] sourcePartly supported

  The Discussion reports defective tight junctions in asthma, and the Results show a disrupted epithelial barrier in CRS, particularly CRS with nasal polyps. The paper mentions reduced barrier function in acute rhinovirus-associated rhinitis, but does not establish it in allergic rhinitis (AR); that part of the claim is unsupported. Page numbers were not provided in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [344] sourceNot checked — no full text of the source

Cough is not induced in patients with rhinitis or healthy controls in simulated models of postnasal drip.

“Interestingly, cough is not induced in patients with rhinitis or healthy controls in simulated models of postnasal drip.349”

• cites [349] sourceSupported

Similarities between AR and asthma extend to innate immunity, including epithelial barrier function and innate lymphoid cells.

“Similarities are not only found in the acquired immune response, but also in the role of innate immunity like epithelial barrier function334 and innate lymphoid cells.332”

• cites [334] sourceNot checked — no full text of the source
• cites [332] sourceSupported

In patients with AR, segmental bronchial or nasal provocation can induce allergic inflammation in both the nasal and bronchial mucosa.

“In patients with AR, segmental bronchial or nasal provocation can induce allergic inflammation in both the nasal and bronchial mucosa.347-349”

• cites [347] sourceNot checked — no full text of the source
• cites [348] sourceNot checked — no full text of the source
• cites [349] sourceCould not verify

  The Discussion (p. 4) mentions nasal secretions collected after provocation, but does not say that provocation induces allergic inflammation in both nasal and bronchial mucosa. The paper examines symptoms after intranasal insertion of simulated mucus; searches for segmental bronchial provocation and bronchial mucosal inflammation found no passage addressing the claimed effect. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

Corticosteroids have not been shown to cause thinning of nasal epithelium.

“Corticosteroids have not, however, been shown to cause thinning of nasal epithelium.322,431”

• cites [322] sourceCould not verify

  The Discussion (pp. 7, 9) reports that intranasal steroids were associated with improved nasal epithelial barrier integrity, but barrier integrity is not epithelial thickness. A search for thinning, atrophy, and epithelial thickness found no passage assessing whether corticosteroids cause thinning. (LLM, conf=0.72)

  Experimental — accuracy not yet measured
• cites [431] sourceNot checked — no full text of the source

Levels of chemokines TARC/CCL17, MDC/CCL22, eotaxin, RANTES, MCP-1, and MIP-1α are elevated after nasal allergen challenge.

“Similarly, levels of chemokines such as thymus-regulated and activation-regulated chemokine (TARC, CCL17), macrophage derived chemokine (MDC, CCL22), eotaxin, RANTES, MCP-1, and macrophage inflammatory protein (MIP)-1α were elevated.388-391”

• cites [388] sourcePartly supported

  The Results section ('Effects of nasal allergen in placebo group compared with baseline'; page not provided) reports post-challenge increases in eotaxin, RANTES, MCP-1, and MIP-1α. The provided passages do not report increases in TARC/CCL17 or MDC/CCL22, so the source supports only four of the six listed chemokines. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [389] sourceNot checked — no full text of the source
• cites [390] sourceNot checked — no full text of the source
• cites [391] sourceNot checked — no full text of the source

Loss-of-function mutations and polymorphisms in genes coding for epithelial barrier markers such as filaggrin are associated with AR and eczema.

“Loss-of-function mutations and polymorphisms in genes coding for epithelial barrier markers such as filaggrin are associated with AR and eczema.427,428”

• cites [427] sourceNot checked — no full text of the source
• cites [428] sourcePartly supported

  The Methods section (page unavailable) lists FLG among genes associated with both allergic rhinitis (AR) and atopic dermatitis (eczema). It specifically links FLG polymorphisms and loss-of-function mutations to increased susceptibility to atopic dermatitis, but does not establish that those variants are associated with AR. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Proteolytic allergens directly disrupt the apical junctional complex via proteolysis, leading to barrier dysfunction.

“Proteolytic allergens directly disrupt the apical junctional complex via proteolysis, leading to barrier dysfunction.430”

• cites [430] sourcePartly supported

  The section on allergen recognition reports that the dust-mite allergen Der p disrupts airway epithelial tight junctions in a protease-dependent manner; the References annotation for study 29 says an allergen protease increased bronchial epithelial permeability. This supports the proposed barrier effect, but the copy does not establish that proteolytic allergens generally disrupt the entire apical junctional complex. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Presence of Clostridium difficile at 1 month of age is associated with increased risk for allergic sensitization (OR 1.54; 95% CI 1.09-2.31) until age 2.

“Penders et al.447 found that the presence of Clostridium difficile at 1 month of age was associated with an increased risk for allergic sensitization (odds ratio [OR] 1.54; 95% confidence interval [CI], 1.09 to 2.31) until the age of 2 years.”

• cites [447] sourcePartly supported

  The Results report that C. difficile colonisation at 1 month was associated with atopic sensitisation within the first 2 years of life, with an adjusted OR of 1.54. The cited confidence interval is incorrect: the Results give 95% CI 1.02–2.31, not 1.09–2.31. No page number is provided in our copy. (LLM, conf=0.93)

  Experimental — accuracy not yet measured

In a United States study of 29,662 children using health care records, the incidence of physician-diagnosed allergic rhinitis during the first year of life was 1%.

“In a study of 29,662 children from the United States that used health care records to follow participants, the incidence of physician-diagnosed AR during the first year of life was 1%.”

• cites [467] sourceSupported

In the Cincinnati Childhood Allergen and Air Pollution Study, 9% of 12-month-old children with a parental history of respiratory allergy met criteria for allergic rhinitis.

“In the Cincinnati Childhood Allergen and Air Pollution Study (CCAAPS), 9% of the 12-month-old children with a parental history of respiratory allergy fulfilled the criteria of AR.465”

• cites [465] sourceSupported

Allergic rhinitis can begin during the first year of life.

“There is evidence that AR may start as early as during the first year of life.”

• cites [465] sourceSupported

Grass pollen, found across Europe, causes wide variations in atopic sensitizations across regions with different climates.

“For instance, grass pollen, which is found across Europe, causes wide variations in atopic sensitizations across regions with different climates.480”

• cites [480]Supported

A meta-analysis of ISAAC-protocol studies including 1,430,329 children aged 0 to 18 years found an overall allergic rhinitis prevalence of 12.66%.

“In a more recent meta-analysis of all studies performed according to the ISAAC-protocol (1,430,329 children aged 0 to 18 years), the overall prevalence of AR was 12.66%.473”

• cites [473] sourceSupported

Most children with allergic rhinitis symptoms early in life have persistent symptoms for several years.

“Most children with symptoms of AR early in life have persistent symptoms for several years.469-471”

• cites [469] sourceNot checked — no full text of the source
• cites [470] sourcePartly supported

  Table E4 (Extended Data) shows that 12 of 19 children with birch-pollen-related allergic rhinitis symptoms at age 4 also had symptoms at ages 8 and 16, supporting persistence in a majority over several years. The cited study examined birch-pollen-related rhinitis in one birth cohort, not allergic rhinitis generally, so the claim is broader than its evidence. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [471] sourceSupported

Smaller studies over more limited geographic regions suggest increased sensitivity rates for perennial allergic rhinitis in urban settings and colder climates.

“Smaller studies over more limited geographic regions that examined PAR suggest increased sensitivity rates in urban settings and colder climates.476-479”

• cites [476] sourceNot checked — no full text of the source
• cites [477] sourcePartly supported

  The Results (section 2, page not provided) report higher overall allergic-rhinitis prevalence in urban than rural Guangzhou, while the Discussion reports a higher proportion of persistent allergic rhinitis in northern than southern regions and suggests climate as a possible explanation. The paper does not establish higher sensitivity rates specifically for perennial allergic rhinitis in either setting; its urban comparison concerns allergic rhinitis overall. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [478] sourceNot checked — no full text of the source
• cites [479] sourceNot checked — no full text of the source

An accompanying GWAS on allergic sensitization showed strong overlap between top hits for sensitization and self-reported allergies.

“In an accompanying GWAS on allergic sensitization, there was strong overlap between top hits for sensitization and self-reported allergies.487,493”

• cites [487] sourceSupported
• cites [493] sourceSupported

The associations of LRRC32 with allergic rhinitis and other allergy-related diseases suggest shared genetic mechanisms.

“These associations suggest shared genetic mechanisms for AR and other allergy-related diseases, evidence further supported by the large-scale GWAS on self-reported cat, HDM, and pollen allergies (as well as AR), which revealed 16 shared susceptibility loci with strong association (p < 5 × 10−8; TLR-locus top hit).487”

• cites [487] sourceSupported

Many candidate genes reported in the literature have not been well replicated across studies and populations.

“However, many of the candidate genes reported in the literature have not been well-replicated across studies and populations.427,504”

• cites [427] sourceNot checked — no full text of the source
• cites [504] sourceSupported

Candidate gene studies have found SNPs in genes involved in antigen presentation (HLA-DQA1), pathogen recognition (TLR2, TLR7, TLR8), and IL signaling and proinflammation (IL13, IL18, TSLP) to be important susceptibility variants for allergic rhinitis.

“Notably, SNPs in genes involved in antigen presentation (for example HLA-DQA1), pathogen recognition (TLR2, TLR7, TLR8), IL signaling and proinflammation (IL13, IL18, and TSLP) are considered important susceptibility variants for AR.496-502”

• cites [496]Not checked — no full text of the source
• cites [497] sourcePartly supported

  The Results section (page unavailable) reports a tentative association between IL13 SNPs and birch-pollen sensitization in Swedish patients with allergic rhinitis. That is narrower than identifying IL13 as an important susceptibility gene for allergic rhinitis. The Methods section (page unavailable) does not list HLA-DQA1, TLR2, TLR7, TLR8, IL18, or TSLP among the genes tested, so this paper does not support those examples. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [498] sourcePartly supported

  The Results report allergic-rhinitis-associated SNPs in the TLR7–TLR8 region in Swedish and Chinese populations. The Background says other studies failed to find an association between TLR2 variants and allergic rhinitis, and this paper does not establish TLR2 as a susceptibility gene. Its evidence therefore supports the TLR7/TLR8 portion of the multi-citation sentence, not the full pathogen-recognition list. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [499] sourceNot checked — no full text of the source
• cites [500] sourcePartly supported

  The Results report that the TLR2 R753Q variant was associated with increased atopic sensitization in German children, supporting the TLR2 portion of the claim. But Table 2 (shown in the indexed Discussion, page unavailable) shows no significant association with hay fever (P = 0.239), so this paper does not establish TLR2 as an allergic-rhinitis susceptibility variant. The other genes in the citing sentence are not attributed specifically to this source. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [501] sourceSupported
• cites [502]Not checked — no full text of the source

Negative studies showed that early exposure to pets represents a risk factor for allergic rhinitis.

“negative studies, (showing that early exposure to pets represents a risk factor for AR523,536-542)”

• cites [523] sourceNot checked — no full text of the source
• cites [536] sourceNot checked — no full text of the source
• cites [537] sourceNot checked — no full text of the source
• cites [538] sourceNot checked — no full text of the source
• cites [539] sourceNot checked — no full text of the source
• cites [540] sourceNot checked — no full text of the source
• cites [541] sourceSupported
• cites [542] sourceNot checked — no full text of the source

A large-scale GWAS on self-reported cat, house dust mite, and pollen allergies, as well as allergic rhinitis, revealed 16 shared susceptibility loci with strong association (p < 5 × 10−8; TLR-locus top hit).

“These associations suggest shared genetic mechanisms for AR and other allergy-related diseases, evidence further supported by the large-scale GWAS on self-reported cat, HDM, and pollen allergies (as well as AR), which revealed 16 shared susceptibility loci with strong association (p < 5 × 10−8; TLR-locus top hit).487”

• cites [487] sourcePartly supported

  The paper’s opening summary (page not specified) reports a GWAS meta-analysis of self-reported cat, dust-mite, and pollen allergy that identified 16 shared loci at P<5×10−8; the TLR1/TLR6/TLR10-region locus has the strongest reported association. But allergic rhinitis was not one of the three phenotypes in that meta-analysis. The paper assessed rhinitis symptoms separately in an exploratory analysis, so the claim overstates its role in the 16-locus finding. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

A significant overlap between susceptibility loci for allergy and autoimmune diseases has been observed.

“In addition to shared genetic effects between different allergy-related diseases, a significant overlap between susceptibility loci for allergy and autoimmune diseases has been observed.495”

• cites [495] sourceSupported

Recent studies show that DNA methylation in children is very strongly influenced by well-known risk factors for allergic diseases such as maternal smoking during pregnancy and air pollution exposure.

“Recent studies show that DNA methylation in children is very strongly influenced by well-known risk factors for allergic diseases such as maternal smoking during pregnancy505 and air pollution exposure.506”

• cites [505] sourceNot checked — no full text of the source
• cites [506] sourcePartly supported

  Citation 506 supports the air-pollution part of the sentence, not the separately cited maternal-smoking part. The Results report associations between prenatal NO2 exposure and methylation at a small number of sites, while the Discussion calls the evidence suggestive. That does not establish that children’s DNA methylation is very strongly influenced by air pollution. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Three studies demonstrated that early exposure to fungal allergens is not associated with allergic rhinitis.

“However, 3 studies demonstrated that early exposure to fungal allergens is not associated with AR.465,542,557”

• cites [465] sourcePartly supported

  The Results (Table 2; page unavailable) show no statistically significant association between visible household mold and allergic rhinitis at age one. The study measured visible mold, not fungal allergen exposure, and its findings do not establish that no association exists. This source contributes one study to the citing sentence’s three-study claim. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [542] sourceNot checked — no full text of the source
• cites [557] sourceNot checked — no full text of the source

No definitive consensus can be drawn regarding the risk-benefit of early inhalant allergen exposure.

“Despite several indepth reviews and a growing body of literature,561-563 no definitive and consensus may be drawn regarding risk-benefit of early inhalant allergen exposure, and further research is welcomed to address the unmet needs on this issue.”

• cites [561] sourceCould not verify

  The 'Putative risk and protective factors' section discusses mixed associations between childhood rhinitis and environmental exposures such as dust endotoxin and mould. It does not assess the risk-benefit of early inhalant allergen exposure or state whether a consensus exists on that question (searched: early inhalant allergen exposure, cat keeping, inhalant). (LLM, conf=0.73)

  Experimental — accuracy not yet measured
• cites [562] sourceNot checked — no full text of the source
• cites [563] sourceSupported

The relationship between sensitization to food allergens and subsequent development of allergic rhinitis during childhood has been investigated in both population-based and high-risk cohorts.

“The relationship between sensitization to food allergens and the subsequent development of AR during childhood has been investigated in both population-based and high-risk cohorts.468,565-568”

• cites [468] sourceNot checked — no full text of the source
• cites [565]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [566] sourceNot checked — no full text of the source
• cites [567] sourceNot checked — no full text of the source
• cites [568] sourceSupported
  Experimental — accuracy not yet measured

Three prospective cohort studies, the highest level of evidence identified for this topic, found no significant correlation between air pollutants and the development of allergic rhinitis.

“However, 3 prospective cohort studies (the highest level of evidence identified for this topic) found no significant correlation.578-580”

• cites [578] sourceSupported
• cites [579] sourceNot checked — no full text of the source
• cites [580] sourceNot checked — no full text of the source

During the 1870s, Blackley found no hay fever among farmers and people living in deprived areas of cities.

“During the 1870s, Blackley found no hay fever among farmers and people living in deprived areas of cities.606”

• cites [606] sourcePartly supported

  In “Hay Fever’s Social Status,” Waite reports that Blackley found no hay-fever symptoms among the “farming classes.” The same passage attributes the negative inquiries in deprived city areas to Beard, not Blackley. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Saulyte et al. found a significant correlation between active smoking and non-allergic or chronic rhinitis.

“However, they did find a significant correlation between active smoking and non-allergic/chronic rhinitis.”

• cites [593] sourcePartly supported

  In Results > Active Smoking (page unavailable), the paper reports a significant association between active smoking and rhinitis under a fixed-effects analysis, but its analysis concerns allergic rhinitis, not non-allergic or chronic rhinitis. The random-effects analysis found no significant overall association with allergic rhinitis; the paper lists a study of nonallergic rhinitis in its References but does not report the claimed finding for that condition. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

A significant positive association between tobacco and the development of non-allergic or chronic rhinitis has been repeatedly identified.

“In contrast, the significant positive association between tobacco and the development of non-allergic/chronic rhinitis has been repeatedly identified.124,128,604”

• cites [124] sourceNot checked — no full text of the source
• cites [128] sourcePartly supported

  The Results and Conclusions report a significant positive association between smoking and rhinitis symptoms in adults, including those without allergic sensitization. The Discussion says this is consistent with another study linking smoking history to chronic sinusitis and nasal congestion. However, this paper examines rhinitis prevalence, not the development of diagnosed non-allergic or chronic rhinitis. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [604] sourcePartly supported

  The Discussion (page unavailable) says epidemiologic studies suggest smoking may contribute to nonallergic rhinitis and reports an association with chronic rhinosinusitis. The Results find a significant association between tobacco exposure and rhinitis prevalence in children without allergic sensitization. The paper does not establish development of nonallergic or chronic rhinitis: its own outcome is prevalent rhinitis symptoms, and chronic rhinosinusitis is a different condition. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Some pediatric studies have identified a positive correlation between increased exposure to various pollutants and an increased diagnosis of allergic rhinitis during childhood.

“Some pediatric studies have identified a positive correlation between increased exposure to various pollutants and an increased diagnosis of AR during childhood.476,557,582-589”

• cites [476] sourceNot checked — no full text of the source
• cites [557] sourceNot checked — no full text of the source
• cites [582] sourceSupported
• cites [583] sourcePartly supported

  The Results (page not provided) report that more frequent truck traffic near homes was associated with rhinitis symptoms in children, and the Discussion reports an association between specific air pollutants and allergic rhinitis in Taiwanese schoolchildren. But this study used reported truck traffic as a proxy for exposure, did not measure pollutant levels, and assessed symptoms rather than an increased rate of diagnosed allergic rhinitis. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [584]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [585] sourceNot checked — no full text of the source
• cites [586] sourceNot checked — no full text of the source
• cites [587] sourceNot checked — no full text of the source
• cites [588] sourceSupported
• cites [589] sourcePartly supported

  The Results (page unavailable) report higher odds of allergic-rhinitis treatment in children with greater exposure to BC, SO2, and NO2. The Statistical methods (page unavailable) say outcomes were identified by questionnaires about symptoms and treatment, not by confirmed diagnoses; the claim’s reference to increased diagnosis is therefore not established by this study. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Studies have shown that tobacco smoke exposure can propagate the development of atopic diseases via mechanisms including direct surface damage to nasal mucosa, altered epigenetic mechanisms through histone acetylation, expression of microRNA, and DNA methylation.

“Studies have shown that tobacco smoke exposure can propagate the development of atopic diseases via several mechanisms including direct surface damage to nasal mucosa, altered epigenetic mechanisms through histone acetylation, expression of microRNA, and DNA methylation.590,591”

• cites [590] sourceSupported
• cites [591] sourceNot checked — no full text of the source

Nicotine may exert an immunosuppressive effect on allergic disease by suppressing eosinophil trafficking and Th2 cytokine/chemokine responses.

“Alternatively, it has also been shown that nicotine may exert an immunosuppressive effect on allergic disease by suppressing eosinophil trafficking and Th2 cytokine/chemokine responses.592”

• cites [592] sourceSupported

The protective effect of breastfeeding seen in children under 5 years of age may have been confounded by the known protective effects of breast milk against viral respiratory infections.

“they do acknowledge that the protective effect of breastfeeding seen in patients less than 5 years of age may have been confounded by known protective effects of breast milk against viral respiratory infections.”

• cites [624] sourceSupported

A 2015 systematic review and meta-analysis found a nonsignificant protective effect of breastfeeding on the development of allergic rhinitis, with an odds ratio of 0.92 and 95% confidence interval 0.84 to 1.01.

“Pooling of estimates from the various studies found a nonsignificant protective effect of breastfeeding on the development of AR (OR 0.92; 95% CI, 0.84 to 1.01).”

• cites [624] sourceSupported

The protective farm effect seems to be stronger when exposed to farm animals and stables.

“The protective farm effect seems to be stronger when exposed to farm animals and stables.522,649-655”

• cites [522] sourceNot checked — no full text of the source
• cites [649] sourceNot checked — no full text of the source
• cites [650] sourceNot checked — no full text of the source
• cites [651] sourceNot checked — no full text of the source
• cites [652] sourcePartly supported

  The Abstract reports protection against atopy in the mixed-farming region but not the crop-farming region, and the ‘Farming and atopy in children’ section suggests that contact with farm animals may explain the difference (page numbers unavailable). The paper does not assess exposure to stables or establish that animal exposure itself makes the protective effect stronger. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [653] sourceNot checked — no full text of the source
• cites [654] sourceNot checked — no full text of the source
• cites [655] sourceNot checked — no full text of the source

There was no association between breastfeeding and allergic rhinitis after 5 years of age, with an odds ratio of 1.05 and 95% confidence interval 0.99 to 1.12.

“However, there was no association after 5 years of age (OR 1.05; 95% CI, 0.99 to 1.12).”

• cites [624] sourceSupported

A large questionnaire study from 31 countries for children aged 6 to 7 years and 52 countries for children aged 13 to 14 years confirmed that the inverse association between number of older siblings and prevalence of hay fever was strongest in more affluent countries.

“A large study based on questionnaire data for children aged 6 to 7 years from 31 countries and 13 to 14 years from 52 countries confirmed that the inverse association between the number of older siblings and prevalence of hay fever was strongest in more affluent countries.646”

• cites [646] sourceSupported

After stratification by age, breastfeeding was associated with a reduced risk of allergic rhinitis in patients under 5 years of age, with an odds ratio of 0.79 and 95% confidence interval 0.63 to 0.98.

“After stratification by age, a reduced risk of AR in patients under 5 years of age was associated with breastfeeding (OR 0.79; 95% CI, 0.63 to 0.98).”

• cites [624] sourceSupported

Two studies from Korea reconfirmed an association between high socioeconomic status and the development of allergic rhinitis.

“More recently, 2 studies from Korea have reconfirmed the previously noted association between high SES and the development of AR.”

• cites [478] sourceNot checked — no full text of the source
• cites [615] sourceSupported

Productivity, practical/activity, emotional, social, and memory function of patients appear to be significantly impacted by allergic rhinitis.

“Furthermore, the productivity, practical/activity, emotional, social, and memory function of patients appear to be significantly impacted by AR.685-689”

• cites [685] sourceNot checked — no full text of the source
• cites [686] sourceNot checked — no full text of the source
• cites [687] sourcePartly supported

  The Abstract reports significant effects on emotional well-being, productivity, and cognitive functioning, and the Results (Burden of AR/C; page not provided) report interference with work or school performance. The copy does not specifically establish effects on social function or memory, and work or school interference does not fully substantiate the broader practical/activity function claim. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [688] sourceNot checked — no full text of the source
• cites [689] sourceNot checked — no full text of the source

Allergen immunotherapy randomized controlled trials with 12 to 18 months of follow-up showed that placebo patients either stayed at their baseline quality-of-life impairment or improved to a lesser degree than treatment arms.

“The AIT RCTs have longer follow-up periods (12 to 18 months) and show similar results, with placebo patients either staying at their baseline QOL impairment, or improving to a lesser degree than the treatment arms.678,679”

• cites [678] sourceNot checked — no full text of the source
• cites [679] sourceSupported

For the adult population, there is level 1b evidence supporting the conclusion that allergic rhinitis negatively impacts sleep.

“For the adult population, there is level 1b evidence supporting the conclusion that AR negatively impacts sleep.705-709”

• cites [705]Not checked — no full text of the source
• cites [706] sourceNot checked — no full text of the source
• cites [707] sourceSupported
• cites [708] sourceNot checked — no full text of the source
• cites [709]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Comorbidities associated with allergic rhinitis, such as rhinosinusitis, Eustachian tube dysfunction, and associated conductive hearing loss, may further contribute to learning dysfunction.

“Comorbidities associated with AR, such as like rhinosinusitis, Eustachian tube dysfunction, and associated conductive hearing loss may further contribute to learning dysfunction.775,776”

• cites [775]Not checked — no full text of the source
• cites [776] sourceSupported

Unnecessary exposure to ionizing radiation carries a risk for future cancer development.

“However, concerns regarding unnecessary exposure to ionizing radiation, with the risk for future cancer development, preclude recommendations for routine use.789,790”

• cites [789]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [790] sourceSupported

PROMs capture several dimensions of the burden AR places on patients.

“Patient reported outcome measures (PROMs) can assess a number of different aspects of how AR affects patients.796”

• cites [796] sourcePartly supported

  The “Significance of PRO Instruments” section says patient-reported outcomes can measure symptoms, physical functioning, psychological and social well-being, and quality of life. The paper supports their ability to assess multiple aspects of a disease’s impact, but it does not discuss AR specifically. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Many validated tools have seen wide use in large trials evaluating AR drug and biologic efficacy.

“Several of these instruments have been used extensively in many large clinical trials to determine the effectiveness of drugs and biologics for treating AR.797-802”

• cites [797] sourcePartly supported

  The Methods describe using TNSS, VAS, and MiniRQLQ to evaluate outcomes in this allergic-rhinitis immunotherapy trial, and the Results report 106 enrolled participants. The paper therefore supports use of several such instruments in a trial, but does not establish that they were used extensively across many large trials of AR drugs and biologics. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [798] sourcePartly supported

  The Methods (Clinical endpoints and assessments; page unavailable) use TNSS and TOSS to evaluate the efficacy of a grass-pollen allergy vaccine. The paper does not establish that several validated instruments were used extensively across many large trials of AR drugs and biologics; its Discussion instead calls for larger studies of this vaccine. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [799] sourceNot checked — no full text of the source
• cites [800] sourceNot checked — no full text of the source
• cites [801] sourceNot checked — no full text of the source
• cites [802] sourceNot checked — no full text of the source

Intradermal estimates fall below recent meta-analytic SPT values: sensitivity 85-88% and specificity 77%.

“This is lower than the pooled estimates of sensitivity (85-88%) and specificity (77%) for SPT, calculated from recent meta-analyses.830,854”

• cites [830] sourceSupported
• cites [854]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

A four-study systematic review found confirmatory intradermal testing after negative SPT had sensitivity 27% (95% CI 10-57) to 50% (CI not calculable) and specificity 69% (95% CI 51-83) to 100% (95% CI 83-100).

“Nevis et al.830 conducted a systematic review of 4 studies to determine the sensitivity and specificity of intradermal testing when used as a confirmatory test following negative SPT. Sensitivity ranged from 27% (95% CI, 10% to 57%) to 50% (sample sizes were too small to calculate CI), while specificity ranged from 69% (95% CI, 51% to 83%) to 100% (95% CI, 83% to 100%).”

• cites [830] sourceSupported

Pimecrolimus does not show any effect on skin whealing responses.

“whereas a study of a similar drug, pimecrolimus, did not show any effect on skin whealing responses.888”

• cites [888] sourceSupported

Skin testing may be preferred over in vitro testing because it allows immediate feedback and visible results.

“First, studies have indicated that while patients are accepting of both in vitro and in vivo allergy testing, skin testing may be preferred because it allows for immediate feedback and visible results.914”

• cites [914] sourceSupported

Total IgE levels are significantly associated with current hay fever in different age classes.

“Salo et al.454 performed a cross-sectional study reporting significant associations between tIgE levels and current hay fever in different age classes.”

• cites [454] sourcePartly supported

  The Results report a statistically significant association between total IgE and current hay fever (adjusted OR 1.86, 95% CI 1.44–2.41) and say that Table II presents age-stratified odds ratios. The available Results passage does not establish that the association was statistically significant in each age class; its explicit age-group comparison concerns current allergies, not hay fever. No page number is available in our copy. (LLM, conf=0.79)

  Experimental — accuracy not yet measured

Measuring total IgE has a favorable role in diagnosing allergic rhinitis, mainly if levels are higher than 100 IU/mL.

“Jacobs et al.900 reported a favorable role of measuring tIgE in diagnosing AR, mainly if levels are higher than 100 IU/mL.”

• cites [900] sourceSupported

Patients with more severe symptoms have been shown to respond better to AIT than those with milder symptoms.

“Given that patients with more severe symptoms have been shown to respond better to AIT than those with milder symptoms, sIgE may help in the selection of candidates for AIT and possibly predict the response.919,924”

• cites [919] sourceSupported
• cites [924] sourceNot checked — no full text of the source

Levels of specific IgE may correlate with severity of allergic rhinitis symptoms.

“A second application lies in the fact that levels of sIgE may correlate with severity of AR symptoms.919-923”

• cites [919] sourceSupported
  Experimental — accuracy not yet measured
• cites [920] sourceNot checked — no full text of the source
• cites [921]Not checked — no full text of the source
• cites [922] sourceSupported
  Experimental — accuracy not yet measured
• cites [923] sourceNot checked — no full text of the source

Intradermal or epicutaneous testing demonstrates higher sensitivity but lower specificity than SPT for several allergens.

“Intradermal or epicutaneous testing demonstrates higher sensitivity but lower specificity than SPT for several allergens.793,856,931,932,944”

• cites [793] sourceNot checked — no full text of the source
• cites [856] sourcePartly supported

  The Abstract describes greater sensitivity as a potential advantage of intradermal testing, while the Discussion (p. 1200) reports that intradermal-positive results were no more predictive of clinical allergy than intradermal-negative results among people with negative skin-prick tests. This supports concern about clinically irrelevant positive intradermal results, but the study does not establish the claimed comparison for epicutaneous testing or for several allergens; its clinical assessment focused on timothy grass. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [931] sourceCould not verify

  The Methods and Results compare skin-prick testing with serum-specific IgE testing, not with intradermal or epicutaneous testing. The Discussion describes discordant results but does not establish the claimed sensitivity–specificity trade-off for those methods (pages unavailable in our copy). (LLM, conf=0.78)

  Experimental — accuracy not yet measured

A positive intradermal reaction to grass pollen in the setting of negative prick testing may not be clinically relevant.

“There is evidence to suggest that a positive intradermal reaction to grass pollen in the setting of negative prick testing may not be clinically relevant.793,856”

• cites [793] sourceNot checked — no full text of the source
• cites [856] sourceSupported

Molecular diagnosis can distinguish cross-reactivity phenomena from true co-sensitization.

“Overall, MD can potentially improve diagnostic accuracy (specificity), distinguish cross-reactivity phenomena from true co-sensitization, resolve low-risk markers from high-risk markers of disease activity, and may improve the indication and selection of suitable allergens for AIT when compared to diagnosis based on SPT and/or sIgE determination with raw commercial extracts.980-984”

• cites [980] sourceNot checked — no full text of the source
• cites [981] sourceNot checked — no full text of the source
• cites [982] sourceNot checked — no full text of the source
• cites [983] sourceSupported
• cites [984] sourceNot checked — no full text of the source

Molecular diagnosis can improve diagnostic specificity compared with diagnosis based on skin prick testing and/or specific IgE using raw commercial extracts.

“Overall, MD can potentially improve diagnostic accuracy (specificity), distinguish cross-reactivity phenomena from true co-sensitization, resolve low-risk markers from high-risk markers of disease activity, and may improve the indication and selection of suitable allergens for AIT when compared to diagnosis based on SPT and/or sIgE determination with raw commercial extracts.980-984”

• cites [980] sourceNot checked — no full text of the source
• cites [981] sourceNot checked — no full text of the source
• cites [982] sourceNot checked — no full text of the source
• cites [983] sourceSupported
  Experimental — accuracy not yet measured
• cites [984] sourceNot checked — no full text of the source

Production of nasal mast cells, eosinophils, and specific IgE rapidly increases after allergen-specific stimulation in the nasal mucosa.

“The production of nasal mast cells, eosinophils, and sIgE rapidly increases after allergen-specific stimulation in the nasal mucosa.288,294,307”

• cites [288] sourcePartly supported

  The “Local IgE in rhinitis” section reports that nasal sIgE increases rapidly after allergen-specific stimulation. It also reports mast-cell and eosinophil activation, not a rapid increase in the production of those cells. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [294] sourceNot checked — no full text of the source
• cites [307] sourceNot checked — no full text of the source

Basophil sensitivity, measured as EC50 or CD-sens, is a marker for the treatment effect of allergen immunotherapy and anti-IgE treatment.

“There is good evidence to suggest that basophil sensitivity (EC50, or eliciting concentration at which 50% of basophils respond; also named CD-sens if it is inverted and multiplied by 100) is a marker for treatment effect of AIT969-971,975-977 and anti-IgE treatment.975”

• Also stated in: § In vitro testing · plain

  “Basophil sensitivity is also useful for measuring response to AIT.”

• cites [969] sourceNot checked — no full text of the source
• cites [970] sourceNot checked — no full text of the source
• cites [971] sourceNot checked — no full text of the source
• cites [975] sourceNot checked — no full text of the source
• cites [976] sourceSupported
• cites [977] sourceNot checked — no full text of the source

Some patients have negative SPT or serum specific IgE despite a clinical history suggestive of allergic rhinitis and meeting ARIA clinical criteria.

“However, some patients have negative SPT or serum sIgE despite a clinical history suggestive of AR and meeting ARIA clinical criteria.101,300”

• cites [101] sourcePartly supported

  Section 6.3.3 states that absence of serum-specific IgE does not preclude symptoms, and section 6.3.7 discusses patients with negative skin tests and serum-specific IgE. The ‘Diagnosis of allergic rhinitis’ section describes typical symptoms, but also says diagnosis depends on concordance between the history and diagnostic tests; it does not establish that patients with negative tests meet ARIA diagnostic criteria. Page numbers are unavailable in our copy. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [300] sourceSupported

Quantification of atopic sensitization using specific IgE level or skin prick test wheal size increases the specificity of allergy tests in relation to the presence and severity of rhinitis.

“Quantification of atopic sensitization by using the level of sIgE antibodies or the size of SPT wheals increases the specificity of allergy tests in relation to the presence and severity of rhinitis.893,1004”

• cites [893] sourceNot checked — no full text of the source
• cites [1004] sourcePartly supported

  The Methods (Definition of variables; page unavailable) use an SPT wheal-size threshold to define atopy, and the Results (Factors associated with rhinitis; page unavailable) report more severe symptoms in children classified as having allergic rather than nonallergic rhinitis. The paper does not report specific IgE levels or show that quantifying either measure increases the specificity of allergy tests for rhinitis presence or severity. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Interpretation of allergy tests has moved from dichotomization based on arbitrary criteria to quantification using specific IgE titer and skin prick test wheal size.

“This has changed the way we interpret the results of allergy tests, with a move from dichotomization (labeling patients as being sensitized based on a “positive” test using arbitrary criteria), to quantification of blood or skin tests using sIgE titer and SPT wheal size.893,1010-1012”

• cites [893] sourceNot checked — no full text of the source
• cites [1010] sourceSupported
• cites [1011] sourcePartly supported

  In “Defining the presence of allergy” (page not provided), the paper says that quantifying specific IgE or skin-test wheal size offers more information than recording the presence or absence of sensitization. It does not describe a historical move away from dichotomization or call the criteria for a positive test arbitrary. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [1012] sourcePartly supported

  In “Attempts to characterize severe asthma in childhood” (page not provided), the paper recommends quantifying skin-test and allergen-specific IgE results in children with severe treatment-resistant asthma and discusses a quantitative relationship in adults. It does not describe a general move away from dichotomizing allergy tests using arbitrary positive-test criteria. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

Molecular diagnosis may improve the indication and selection of suitable allergens for allergen immunotherapy compared with skin prick testing and/or specific IgE using raw commercial extracts.

“Overall, MD can potentially improve diagnostic accuracy (specificity), distinguish cross-reactivity phenomena from true co-sensitization, resolve low-risk markers from high-risk markers of disease activity, and may improve the indication and selection of suitable allergens for AIT when compared to diagnosis based on SPT and/or sIgE determination with raw commercial extracts.980-984”

• cites [980] sourceNot checked — no full text of the source
• cites [981] sourceNot checked — no full text of the source
• cites [982] sourceNot checked — no full text of the source
• cites [983] sourceSupported
• cites [984] sourceNot checked — no full text of the source

Blo t 5 is a marker of sensitization to Blomia tropicalis.

“and Blo t 5 for Blomia tropicalis (non-Pyroglyphidae mite).990”

• cites [990] sourceSupported
  Experimental — accuracy not yet measured

Molecular diagnosis can separate low-risk markers from high-risk markers of disease activity.

“Overall, MD can potentially improve diagnostic accuracy (specificity), distinguish cross-reactivity phenomena from true co-sensitization, resolve low-risk markers from high-risk markers of disease activity, and may improve the indication and selection of suitable allergens for AIT when compared to diagnosis based on SPT and/or sIgE determination with raw commercial extracts.980-984”

• cites [980] sourceNot checked — no full text of the source
• cites [981] sourceNot checked — no full text of the source
• cites [982] sourceNot checked — no full text of the source
• cites [983] sourceSupported
• cites [984] sourceNot checked — no full text of the source

Allergen sensitization does not necessarily imply clinical responsiveness.

“Nevertheless, all in vitro test results should be evaluated alongside the clinical history, since allergen sensitization does not necessarily imply clinical responsiveness.”

• cites [1009] sourceNot checked — no full text of the source
• cites [1010] sourceSupported

Results from singleplex and multiplex platforms for measuring IgE are not interchangeable.

“Results of singleplex and multiplex platforms are not interchangeable.”

• cites [983] sourceSupported

Distinct patterns of IgE responses to different protein families are associated with different clinical symptoms.

“and distinct patterns of IgE responses to different protein families are associated with different clinical symptoms.”

• cites [1018] sourceSupported
• cites [1019] sourceSupported
  Experimental — accuracy not yet measured

Numerous randomized, placebo-controlled clinical trials using allergen challenge chambers have tested the efficacy of drugs with immediate therapeutic activity, such as antihistamines, or with prophylactic therapeutic potential, such as topical steroids, novel anti-inflammatory compounds, or probiotics.

“In this respect, numerous randomized, placebo-controlled clinical trials have been conducted using parallel-group or crossover designs in order to test the efficacy of drugs with immediate therapeutic activity, such as antihistamines,1050-1053 or with prophylactic therapeutic potential, such as topical steroids,1054-1056 novel anti-inflammatory compounds,1057-1060 or probiotics.1061”

• cites [1050] sourceNot checked — no full text of the source
• cites [1051] sourceSupported
• cites [1052] sourceNot checked — no full text of the source
• cites [1053] sourceNot checked — no full text of the source
• cites [1054] sourceNot checked — no full text of the source
• cites [1055] sourceNot checked — no full text of the source
• cites [1056] sourceNot checked — no full text of the source
• cites [1057] sourceNot checked — no full text of the source
• cites [1058] sourceSupported
• cites [1059] sourceNot checked — no full text of the source

Different subtypes of atopy are characterized by a unique pattern of responses to different allergens and the timing of onset of allergen-specific sensitization.

“Different subtypes of atopy are characterized by a unique pattern of the responses to different allergens and the timing of onset of allergen-specific sensitization.1023”

• cites [1023] sourceSupported

Allergen challenge chambers have been intensively used in phase II clinical drug development to study dose-finding, onset of action, and duration of action.

“With the given level of technical and clinical validation, ACCs have been intensively used in clinical drug development to study pharmacological properties of new drugs during phase II trials, such as dose-finding,1039-1041 onset of action,1042-1046 and duration of action.1047-1049”

• cites [1039] sourceSupported
• cites [1040]Not checked — no full text of the source
• cites [1041] sourceNot checked — no full text of the source
• cites [1042] sourceNot checked — no full text of the source
• cites [1043]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [1044] sourceNot checked — no full text of the source
• cites [1045] sourceNot checked — no full text of the source
• cites [1046] sourceNot checked — no full text of the source
• cites [1047]Not checked — no full text of the source
• cites [1048] sourceNot checked — no full text of the source

The risk of allergic disease increases with an increasing number of sensitizations to individual allergenic proteins.

“The risk of allergic disease increases with the increasing number of sensitizations to individual allergenic proteins, and IgE polysensitization to several HDM molecules strongly predicts rhinitis.1019,1020”

• cites [1019] sourcePartly supported

  The ‘Association between longitudinal sensitization trajectories and clinical outcomes’ section reports that children with complete mite-component sensitization had the highest odds of asthma and were the only mite group significantly associated with comorbid asthma, rhinitis, and eczema. It does not establish a general, stepwise increase in allergic-disease risk with each additional protein sensitization; associations varied by allergen and outcome. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [1020] sourceNot checked — no full text of the source

Measuring sensitization to individual allergen molecules in component resolved diagnosis may be more informative than standard tests using whole-allergen extracts.

“Measuring sensitization to individual allergen molecules in a CRD may more be informative than standard tests using whole-allergen extracts.470,1014-1016”

• cites [470] sourceSupported
• cites [1014] sourceNot checked — no full text of the source
• cites [1015] sourceNot checked — no full text of the source
• cites [1016] sourceSupported

Many allergen challenge chambers have been intensively validated for specificity and dose-dependency of symptom induction, temporal stability, and spatial homogeneity of allergen exposure.

“Many ACCs have been intensively validated regarding specificity and dose-dependency of symptom induction as well as technical aspects such as temporal stability and spatial homogeneity of the allergen exposure.1029-1037”

• cites [1029] sourcePartly supported

  The Results report stronger symptoms at 3500 than at 2500 grains/m³ and no symptoms in non-atopic controls. The Introduction describes sampling throughout the EEU and maintaining pollen concentrations within a narrow range. These passages support validation of the EEU, but not the claim that many chambers have been intensively validated for all the listed properties; the Discussion notes that not all other facilities have published validation work. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [1030] sourcePartly supported

  The Results (page unavailable) show that birch-allergic participants developed substantially greater symptoms than non-allergic participants, supporting specificity of symptom induction. The Methods describe maintaining a target pollen concentration and adjusting delivery using samplers at seven locations, supporting temporal and spatial control of exposure. The study used one target concentration in one chamber, however, so it does not establish dose-dependency or itself validate many chambers. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [1031]Not checked — no full text of the source
• cites [1032] sourceNot checked — no full text of the source
• cites [1033] sourceNot checked — no full text of the source
• cites [1034] sourceNot checked — no full text of the source
• cites [1035] sourceNot checked — no full text of the source
• cites [1036] sourceNot checked — no full text of the source
• cites [1037] sourceNot checked — no full text of the source

Patterns of component-specific IgE responses to multiple allergenic proteins have reasonable discrimination ability for rhinoconjunctivitis.

“The patterns of component-specific IgE responses to multiple allergenic proteins have a reasonable discrimination ability for rhinoconjuinctivitis,1017”

• cites [1017] sourceSupported

IgE polysensitization to several house dust mite molecules strongly predicts rhinitis.

“The risk of allergic disease increases with the increasing number of sensitizations to individual allergenic proteins, and IgE polysensitization to several HDM molecules strongly predicts rhinitis.1019,1020”

• cites [1019] sourceSupported
  Experimental — accuracy not yet measured
• cites [1020] sourceNot checked — no full text of the source

Allergic rhinitis is commonly diagnosed by the combination of clinical history and results of in vivo and/or in vitro tests for specific IgE antibodies.

“AR is commonly diagnosed by the combination of clinical history and results of in vivo and/or in vitro tests for sIgE antibodies.1090”

• cites [1090] sourceCould not verify

  The AR phenotypes section describes allergic rhinitis as IgE-mediated, and the Epidemiology section mentions diagnosis and a separate guide to skin-prick testing. Neither passage says that diagnosis commonly combines clinical history with in vivo or in vitro specific-IgE test results; searches for those diagnostic terms found no passage establishing the combination. (LLM, conf=0.70)

  Experimental — accuracy not yet measured

A recent systematic review published in the European Academy of Allergy and Clinical Immunology guidelines for daily practice of conjunctival provocation testing found grade B evidence for the capacity to individuate the allergen trigger.

“A very recent systematic review was performed and the results were published in the EAACI guidelines for daily practice of CPT, with grade B evidence for the capacity to individuate the allergen trigger.1082”

• cites [1082] sourcePartly supported

  The Methods section describes a review of diagnostic studies, and the Rationale and definitions and CPT sections support using conjunctival provocation to assess whether a specific allergen produces ocular symptoms. However, the passages do not assign grade B evidence to that capacity. Page numbers are unavailable in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Environmental control measures have been advocated as a management strategy for allergic rhinitis, with evaluation of both physical barriers and chemical treatments.

“HDMs represent 1 of the most common triggers of AR,1114 and EC measures have been advocated as a management strategy, with evaluation of both physical barriers and chemical treatments.1114-1118”

• cites [1114] sourceNot checked — no full text of the source
• cites [1115]Not checked — no full text of the source
• cites [1116] sourcePartly supported

  The Treatment—Allergen avoidance section says that avoiding house dust mites may control perennial allergic rhinitis, supporting environmental control as a management strategy. It does not discuss or evaluate physical barriers or chemical treatments. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [1117] sourceSupported
• cites [1118] sourceNot checked — no full text of the source

Nasal provocation testing with mites, pollens, and Alternaria was positive in 100% of 22 adults with previously diagnosed local allergic rhinitis.

“NPT with mites, pollens and Alternaria was positive in 100% of 22 adults with previously diagnosed LAR,1079”

• cites [1079] sourceSupported

Various physical techniques have been evaluated for the treatment of allergic rhinitis, with variable findings.

“Various physical techniques (eg, heating, ventilation, freezing, barrier methods, air filtration, vacuuming, and ionizers) have been evaluated for the treatment of AR, with variable findings.”

• cites [1114] sourceNot checked — no full text of the source
• cites [1115]Not checked — no full text of the source
• cites [1116] sourcePartly supported

  The Treatment—Allergen avoidance passage (page not specified in our copy) says avoidance measures may control house-dust-mite-related perennial allergic rhinitis. It does not identify the listed physical techniques or report that they were evaluated with variable findings. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [1117] sourcePartly supported

  In “Controlling concentrations of mite allergens—Bedrooms” (page not supplied), the paper reports clinical benefit from effective mite avoidance in patients with perennial rhinitis. It discusses the listed physical techniques and their differing results, but most of those assessments concern asthma or allergen reduction rather than treatment outcomes for allergic rhinitis. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [1118] sourceNot checked — no full text of the source

Integrated home management consisting of professional cleaning, education, and pest control is not economically sustainable.

“As the expense of integrated home management consisting of professional cleaning, education, and pest control is not economically sustainable, investigations are focused on assessing the efficacy of single interventions, such as extermination alone, to assess possible cost benefits.1135,1143”

• cites [1135] sourcePartly supported

  The Discussion (page unavailable) says the comprehensive intervention costs much more than extermination alone and calls for testing whether extermination alone can reduce allergens. It does not say that the combined approach is economically unsustainable; that conclusion is stronger than the source supports. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [1143] sourceNot checked — no full text of the source

Bait traps plus labor and monitoring costs were less expensive than multiple commercial applications of insecticide sprays to baseboards and cracks.

“When cost was considered, the price of bait traps along with labor and monitoring costs were found to be less expensive than multiple commercial applications of insecticide sprays to baseboards and cracks.1133”

• cites [1133] sourceSupported

It is difficult to dramatically reduce cockroach allergen levels in the home unless a significant reduction in cockroach counts is maintained over time.

“Thus it is difficult to dramatically reduce cockroach allergen levels in the home unless a significant reduction in cockroach counts is maintained over time.1133”

• cites [1133] sourceSupported

Even when cockroach count and Bla g1 and Bla g2 levels were reduced by home interventions, cockroach allergen levels after treatment often remained higher than acceptable median levels associated with clinical benefits in sensitized individuals.

“Even though cockroach count and Bla g1 and Bla g2 allergen levels were reduced in many studies with home interventions, the level of cockroach allergen following treatment remained higher than acceptable median levels associated with clinical benefits in sensitized individuals.1134,1137-1140”

• cites [1134] sourceNot checked — no full text of the source
• cites [1137] sourceNot checked — no full text of the source
• cites [1138] sourceNot checked — no full text of the source
• cites [1139] sourceNot checked — no full text of the source
• cites [1140] sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

The objective findings of improved nasal airway resistance suggest that the H2 histamine receptor modulates nasal tissue response to histamine.

“The objective findings of improved nasal airway resistance suggest that the H2 histamine receptor does modulate nasal tissue response to histamine.1193-1195”

• cites [1193] sourceNot checked — no full text of the source
• cites [1194] sourcePartly supported

  The Results and Discussion report that ranitidine reduced histamine-induced nasal blockage in one experiment, supporting a possible H2 role, but its effects were variable across experiments. The Measurement of nasal patency section says the objective measure was minimum nasal cross-sectional area by acoustic rhinometry, not nasal airway resistance. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [1195] sourceNot checked — no full text of the source

Most ILIT trials used commercially available grass pollen or birch pollen allergen extract as the antigen.

“Most trials1716,1718-1721 used commercially available grass pollen or birch pollen allergen extract as the antigen.”

• cites [1716] sourceNot checked — no full text of the source
• cites [1718] sourceNot checked — no full text of the source
• cites [1719] sourceSupported
• cites [1720] sourceNot checked — no full text of the source
• cites [1721] sourceNot checked — no full text of the source

In that trial, patients in the treatment arm had improvement in subjective symptom scores after the 2006 (p = 0.02) and 2007 (p = 0.005) pollen seasons.

“Patients in the treatment arm had improvement in subjective symptom scores, both after the pollen seasons of 2006 (p = 0.02) and 2007 (p = 0.005).”

• cites [1712] sourceSupported

In that fourth trial, there was no change in combined symptom and medication scores.

“There was no change in combined symptom and medication scores.”

• cites [1715] sourcePartly supported

  The results passage (indexed under Abstract; page unavailable) reports no difference in the combined symptom and medication score between the allergen and placebo groups. That does not establish that the score did not change over time. The paper also describes the study as its third trial, not a fourth trial. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

In that fourth trial, eight systemic reactions led to study exclusion.

“Eight systemic reactions led to study exclusion.”

• cites [1715] sourceSupported

In that trial, improvement of nasal provocation test scores was not significantly better in treatment vs placebo groups.

“However, the improvement of nasal provocation test scores was not significantly better in the treatment vs placebo groups.”

• cites [1712] sourceSupported

Clinical trials show that AR symptom reduction can be achieved with only 3 doses of injected allergen at 1-month intervals.

“Clinical trials have illustrated that a reduction in AR symptoms can be achieved with just 3 doses of injected allergen, with a dosage interval of 1 month1716-1720 (Table IX.D.6).”

• cites [1716] sourceNot checked — no full text of the source
• cites [1717] sourceNot checked — no full text of the source
• cites [1718] sourceNot checked — no full text of the source
• cites [1719] sourceSupported
• cites [1720] sourceNot checked — no full text of the source

Of 6 ILIT trials published so far, 5 demonstrated clinical efficacy and safety.

“Of the 6 trials published thus far, 5 have demonstrated clinical efficacy and safety.1716-1720”

• cites [1716] sourceNot checked — no full text of the source
• cites [1717] sourceNot checked — no full text of the source
• cites [1718] sourceNot checked — no full text of the source
• cites [1719] sourceSupported
• cites [1720] sourceNot checked — no full text of the source

In that trial, combination therapy reduced the median rescue medication score by 80% compared with AIT alone.

“and 80% reduction in median rescue medication score.”

• cites [1400] sourceSupported
  Experimental — accuracy not yet measured

Omalizumab pretreatment improves the safety of AIT for food or insect venom hypersensitivity.

“Additional study of AIT for the treatment of food1739 or insect venom1740,1741 hypersensitivity has also demonstrated improved safety with omalizumab pretreatment.”

• cites [1739] sourcePartly supported

  The citation is attached to food hypersensitivity, not insect venom. In the Study design and Safety sections (pages not supplied), the paper reports omalizumab pretreatment followed by food oral immunotherapy, with most reactions mild. But it had no untreated comparison group, and its conclusion calls for trials with and without omalizumab; it therefore does not demonstrate that pretreatment improved safety. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [1740] sourceNot checked — no full text of the source
• cites [1741]Not checked — no full text of the source

In the OMIT versus SLIT pilot study, there were no significant differences between outcome measures for the two treatment arms.

“No adverse events were reported, and there were no significant differences between outcome measures for both treatment arms.1729”

• cites [1729] sourceSupported

Other large studies found a link between the severity and/or control of asthma and rhinitis in children and adults.

“Other large studies found a link between the severity and/or control of both diseases in children and adults.1754-1758”

• cites [1754] sourceNot checked — no full text of the source
• cites [1755] sourceNot checked — no full text of the source
• cites [1756]Supported
• cites [1757] sourceNot checked — no full text of the source
• cites [1758] sourceNot checked — no full text of the source

In vitro, combination therapy inhibited allergen-specific IgE binding for 42 weeks after discontinuation, compared with 30 weeks for omalizumab alone.

“An unrelated study by Klunker et al.1734 provides further evidence for the efficacy of combination therapy, with in vitro demonstration of inhibition of allergen-specific IgE binding for 42 weeks after discontinuation of combination therapy (vs 30 weeks with omalizumab alone).”

• cites [1734] sourceSupported

Some studies showed that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects.

“Some of these studies showed that rhinitis is a significant risk factor for adult-onset asthma in both atopic and nonatopic subjects.1779,1780,1783”

• cites [1779] sourceSupported
• cites [1780] sourceNot checked — no full text of the source
• cites [1783] sourceNot checked — no full text of the source

There is evidence that AR therapies including INCS, oral antihistamines, LTRAs, and AIT may benefit both AR and asthma.

“However, there is a body of evidence to suggest that AR therapies, including INCS,1296,1788-1790 oral antihistamines,1791,1792 LTRAs,7,1793,1794 and AIT1672,1788,1795,1796 may benefit both conditions.”

• cites [1296] sourceNot checked — no full text of the source
• cites [1788] sourceNot checked — no full text of the source
• cites [1789] sourceSupported
• cites [1790] sourceNot checked — no full text of the source
• cites [1791]Not checked — no full text of the source

Rhinitis is a risk factor independent of allergy for developing asthma in both adults and children.

“Therefore, rhinitis is a risk factor independent of allergy for developing asthma in both adults1779,1780,1783 and children.597”

• cites [1779] sourceSupported
• cites [1780] sourceNot checked — no full text of the source
• cites [1783] sourceNot checked — no full text of the source

A Cochrane review of randomized trials found no benefit of chemical or physical methods to reduce house dust mite allergen in subjects with asthma.

“A Cochrane review examining randomized trials of subjects with asthma who underwent chemical or physical methods to reduce HDM allergen found no benefit with these methods.1799”

• cites [1799] sourceSupported

Outdoor or indoor air pollution remains debated as a risk factor for AR or NAR.

“Outdoor or indoor air pollution is still a matter of debate as risk factor for AR or NAR.101”

• cites [101] sourceSupported

Single allergen avoidance or elimination plans such as removing or washing pets, mattress coverings, removing carpeting, and HEPA filters have shown limited evidence-based clinical benefit for reducing asthma and/or AR symptoms.

“Single allergen avoidance or elimination plans such as removing or washing pets, mattress coverings, removing carpeting, and use of HEPA filters have shown limited evidence-based clinical benefit for reducing asthma and/or AR symptoms.101,1799,1800”

• cites [101] sourceSupported
• cites [1799] sourcePartly supported

  In the reply’s discussion of the review (page not provided), the authors report no clinical effect from measures aimed at reducing house dust mite exposure in patients with asthma. That supports the claim for mite-control measures and asthma, but the reply does not establish limited benefit for removing or washing pets, carpeting removal, HEPA filters, or allergic rhinitis symptoms. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [1800] sourceNot checked — no full text of the source

LTRAs are the only class of medications specifically described in the 2008 AR management guide and full ARIA report as effective for both asthma and AR.

“In fact, the LTRAs are the only class of medications specifically described in the 2008 AR management guide for primary care physicians, and in the full ARIA report, as effective for both asthma and AR.101,1814”

• cites [101] sourcePartly supported

  Table 24 in section 7.8.2 describes antileukotrienes as “Effective on asthma and rhinitis,” and the Pharmacodynamics section reports that montelukast improved nasal and bronchial symptoms. Our copy does not establish that LTRAs are the only medication class so described, or verify what the separate primary-care management guide says. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [1814] sourceNot checked — no full text of the source

A 2003 Cochrane review found no significant improvement in asthma outcomes with INCS in patients with coexistent rhinitis.

“A 2003 Cochrane review evaluated the efficacy of INCS on asthma outcomes in patients with coexistent rhinitis, finding no significant improvement in asthma outcomes with the use of INCS.1295”

• cites [1295] sourceSupported

A 2015 review identified some utility of LTRAs for patients with concomitant AR and asthma.

“A more recent review in 2015 also identified some utility of LTRAs for patients with concomitant AR and asthma.1802”

• cites [1802] sourceSupported

Exposure to allergens in allergic patients is associated with increased eosinophilia in the maxillary sinus.

“Exposure to allergens in allergic patients has been associated with increased eosinophilia in the maxillary sinus.1844,1845”

• cites [1844] sourceSupported
• cites [1845] sourceNot checked — no full text of the source

The efficacy of sublingual immunotherapy for allergic rhinitis has been confirmed by several systematic reviews.

“The efficacy of SLIT for AR has been confirmed by several systematic reviews.1694,1695,1823”

• cites [1694] sourceNot checked — no full text of the source
• cites [1695] sourceNot checked — no full text of the source
• cites [1823] sourceSupported

Omalizumab has acceptable safety for use up to 52 weeks.

“There is evidence for acceptable safety for use up to 52 weeks.1821”

• cites [1821] sourceSupported

A second study identified upregulation of toll-like receptor 9 expression, suggesting increased resistance to bacterial infection rather than susceptibility.

“The second study identified an upregulation in toll-like receptor 9 expression, suggesting increased resistance to bacterial infection rather than susceptibility.1853”

• cites [1853] sourcePartly supported

  The Discussion reports increased TLR9 expression in allergic rhinitis patients with recurrent acute sinusitis, and the Conclusion suggests it may be a compensatory antimicrobial response rather than an ongoing defect that increases susceptibility. The paper links this response to recovery from episodes, but does not establish increased resistance to acquiring bacterial infection; it notes that infections recur and the effect may be short-lived (Conclusion; page not provided). (LLM, conf=0.85)

  Experimental — accuracy not yet measured

As many as 70% of patients with birch allergy will manifest a food-related sensitivity.

“As many as 70% of patients with birch allergy will manifest a food-related sensitivity.1917”

• cites [1917] sourcePartly supported

  The “ANTIGENS CAUSING OAS” section says that more than 70% of patients with birch pollinosis in Europe are allergic to pollen-related foods. This supports a high rate of food-related allergy, but the citing sentence omits the European setting and describes 70% as an upper figure rather than saying more than 70%. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

In 155 children referred from Pediatric Allergy to Otolaryngology, a negative correlation was observed between adenoid hypertrophy and allergen positivity (r = -0.208, p = 0.009).

“They observed a negative correlation between AH and allergen positivity (r = −0.208, p = 0.009).1941”

• cites [1941] sourceSupported

In one study, cooked apple, carrot, or celery did not cause oral allergy symptoms in patients with atopic dermatitis and birch pollen allergy who had oral allergy syndrome and dermatologic symptoms upon ingestion of the raw foods.

“Cooked versions of the offending foods did not cause oral allergy symptoms.1922”

• cites [1922] sourceSupported

Some patients in that study manifested a late eczematous skin reaction, likely T-cell-mediated.

“However, some patients did manifest a late eczematous skin reaction, which was likely T-cell–mediated (Table X.E-2).”

• cites [1922] sourceSupported
  Experimental — accuracy not yet measured

Randomized placebo-controlled trials have shown that intranasal corticosteroids do not improve otitis media with effusion outcomes.

“randomized placebo-controlled trials have shown that INCS do not improve OME outcomes.1971-1973”

• cites [1971] sourceNot checked — no full text of the source
• cites [1972]Not checked — no full text of the source
• cites [1973] sourceSupported

Several studies reported higher Voice Handicap Index scores in allergic rhinitis patients compared with control subjects.

“Several studies have reported higher Voice Handicap Index (VHI) scores in patients with AR compared to control subjects.1996-1999”

• cites [1996] sourceNot checked — no full text of the source
• cites [1997] sourceSupported
• cites [1998] sourceNot checked — no full text of the source
• cites [1999] sourceNot checked — no full text of the source