Impact of Tobacco Smoke and Nicotine Exposure on Lung Development

Prenatal exposure of children to tobacco smoke remains high in the United States and worldwide.

“Prenatal exposure of children to tobacco smoke remains high in the United States and worldwide, and caregiver questionnaires may underrepresent the actual number of children exposed to SHS. 6”

• cites [6] Collaco, 2015, Hair nicotine levels in children with bronchopulmonary dysplasia, Pediatrics sourcePartly supported

  The Hair Nicotine Levels section reports that 21 of 93 children whose caregivers reported no household smoker had hair nicotine above the exposure cutoff, supporting the concern that questionnaires may miss exposed children. The study concerns young children with bronchopulmonary dysplasia; its Demographics section reports maternal smoking during pregnancy for three subjects, but it does not establish that prenatal tobacco-smoke exposure remains high in the United States or worldwide. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Tobacco smoke exposure can adversely affect lung development.

“Tobacco smoke exposure can adversely affect lung development, cause small airway dysfunction and wheeze, and increase the frequency of upper and lower respiratory tract illnesses.[16][17][18]”

• cites [16] Suzuki, 2009, Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam, Thorax sourceCould not verify

  The Significance of study section discusses smoke-related damage to respiratory defenses, and the Abstract discusses childhood respiratory illness, but neither addresses lung development. Searches for lung development and lung growth found no passage establishing that point in our copy. (LLM, conf=0.72)

  Experimental — accuracy not yet measured
• cites [17] Kalliola, 2013, Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze, J Allergy Clin Immunol sourceNot checked — no full text of the source
• cites [18] Charoenca, 2013, Determining the burden of secondhand smoke exposure on the respiratory health of Thai children, Tob Induc Dis sourceSupported

Caregiver questionnaires may underrepresent the actual number of children exposed to SHS.

“Prenatal exposure of children to tobacco smoke remains high in the United States and worldwide, and caregiver questionnaires may underrepresent the actual number of children exposed to SHS. 6”

• cites [6] Collaco, 2015, Hair nicotine levels in children with bronchopulmonary dysplasia, Pediatrics sourceSupported

SHS exposure may impair the effectiveness of corticosteroids used for the treatment of small airway disease.

“SHS exposure may also impair the effectiveness of corticosteroids used for the treatment of small airway disease.21”

• cites [21] Cohen, 2010, In utero smoke exposure and impaired response to inhaled corticosteroids in children with asthma, J Allergy Clin Immunol sourcePartly supported

  The Results and Discussion report that children with asthma exposed to tobacco smoke in utero had a blunted response to inhaled budesonide. The claim extends that finding to SHS exposure generally and to treatment of small airway disease, neither of which the study establishes; current environmental tobacco smoke exposure was adjusted for, not identified as the exposure driving the result. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Adverse health effects caused by SHS may be augmented in children with a genetic susceptibility to asthma.

“In addition, adverse health effects caused by SHS may be augmented in children with a genetic susceptibility to asthma, and exposure to tobacco smoke during in utero life may cause epigenetic changes in fetal lung.22”

• cites [22] Chhabra, 2014, Fetal lung and placental methylation is associated with in utero nicotine exposure, Epigenetics sourcePartly supported

  The Results and Discussion report an association between in utero nicotine exposure and altered DNA methylation in fetal lung, supporting the sentence’s epigenetic-change possibility. The paper does not establish that secondhand smoke has greater adverse effects in children genetically susceptible to asthma; its Introduction discusses prenatal smoke and asthma generally, while genotype appears in a reference title. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Exposure to tobacco smoke during in utero life may cause epigenetic changes in fetal lung.

“In addition, adverse health effects caused by SHS may be augmented in children with a genetic susceptibility to asthma, and exposure to tobacco smoke during in utero life may cause epigenetic changes in fetal lung.22”

• cites [22] Chhabra, 2014, Fetal lung and placental methylation is associated with in utero nicotine exposure, Epigenetics sourceSupported

Childhood pneumonia is associated with diminished adult lung function.

“However, recently Chan and colleagues 19 found an association between childhood pneumonia and diminished adult lung function.”

• cites [19] Chan, 2015, Pneumonia in childhood and impaired lung function in adults: a longitudinal study, Pediatrics sourceSupported

The detrimental effects of childhood tobacco smoke exposure on respiratory health may be increased by confounding factors including psychosocial stress, lower socioeconomic status, underlying chronic lung disease, genetic polymorphisms, and exposure to environmental pollutants.

“The detrimental effects of childhood tobacco smoke exposure on respiratory health may be increased by other confounding factors, including psychosocial stress, lower socioeconomic status, underlying chronic lung disease, genetic polymorphisms, and exposure to environmental pollutants.20”

• cites [20] Brehm, 2015, Stress and bronchodilator response in children with asthma, Am J Respir Crit Care Med sourcePartly supported

  The At a Glance Commentary and Abstract report that stress and an ADCYAP1R1 polymorphism are associated with reduced bronchodilator response in children with asthma. The Abstract says the analysis adjusted for environmental tobacco smoke; it does not show that stress or the polymorphism increases the respiratory harm from tobacco exposure. The cited passages also do not establish that lower socioeconomic status, chronic lung disease, or pollutants amplify that harm. Page numbers were not provided for these passages. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Tobacco smoke exposure can increase the frequency of upper and lower respiratory tract illnesses.

“Tobacco smoke exposure can adversely affect lung development, cause small airway dysfunction and wheeze, and increase the frequency of upper and lower respiratory tract illnesses.[16][17][18]”

• cites [16] Suzuki, 2009, Association of environmental tobacco smoking exposure with an increased risk of hospital admissions for pneumonia in children under 5 years of age in Vietnam, Thorax sourcePartly supported

  The Results report more pneumonia hospital admissions among children under 5 exposed to environmental tobacco smoke, supporting an association with a lower respiratory tract illness. The paper also discusses respiratory tract infections generally, but our copy does not establish an increased frequency of upper respiratory tract illnesses; its measured outcome was pneumonia admission. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [17] Kalliola, 2013, Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze, J Allergy Clin Immunol sourceNot checked — no full text of the source
• cites [18] Charoenca, 2013, Determining the burden of secondhand smoke exposure on the respiratory health of Thai children, Tob Induc Dis sourcePartly supported

  The Abstract Conclusions and Discussion link secondhand smoke exposure in Thai children to a greater risk of acute lower respiratory conditions. The paper does not establish an increase in upper respiratory illnesses or measure how frequently either type of illness occurs. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Nicotine exposure causes differentiation of nonhuman primate embryonic stem cells into fibroblasts.

“In their study, exposure of nicotine caused downregulation of n-Myc expression and differentiation of nonhuman primate embryonic stem cells into fibroblasts, demonstrating that exposure to nicotine during embryogenesis can affect embryonic stem cell differentiation.”

• cites [29] Ben-Yehudah, 2013, Nicotine exposure during differentiation causes inhibition of N-myc expression, Respir Res sourcePartly supported

  The Results (Abstract; no page given) report that nonhuman primate embryonic stem cells differentiated into fibroblasts in the presence of nicotine, with reduced N-myc expression. But the Methods (In Vitro differentiation; no page given) describe a directed differentiation protocol used for both treated and untreated cells. The paper supports nicotine altering differentiation, not nicotine exposure causing the cells to differentiate into fibroblasts. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Offspring of smoking mothers who received vitamin C during in utero life had better airflow and less wheezing through the first year of life compared with offspring of untreated mothers who smoked during pregnancy.

“A recent randomized placebo-controlled study found that the offspring of smoking mothers who received vitamin C during in utero life had better airflow and less wheezing through the first year of life compared with those of untreated mothers who smoked during pregnancy.43”

• cites [43] McEvoy, 2014, Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial, JAMA sourcePartly supported

  The Results report improved pulmonary function in newborns of smokers randomized to vitamin C and less wheezing through the first year compared with the placebo group. But the Secondary Outcomes section reports no significant difference in pulmonary function at one year, so the source does not establish better airflow throughout that year. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Prenatal nicotine exposure in mice leads to diminished forced expiratory flows in adulthood.

“Prenatal nicotine exposure in mice has been shown to lead to diminished forced expiratory flows in adulthood, but interestingly not in a7 nAChR knockout mice.38”

• cites [38] Wongtrakool, 2012, Prenatal nicotine exposure alters lung function and airway geometry through alpha7 nicotinic receptors, Am J Respir Cell Mol Biol sourceSupported

Prenatal nicotine exposure in mice does not lead to diminished forced expiratory flows in adulthood in a7 nAChR knockout mice.

“Prenatal nicotine exposure in mice has been shown to lead to diminished forced expiratory flows in adulthood, but interestingly not in a7 nAChR knockout mice.38”

• cites [38] Wongtrakool, 2012, Prenatal nicotine exposure alters lung function and airway geometry through alpha7 nicotinic receptors, Am J Respir Cell Mol Biol sourceSupported

Rodent studies indicate that nicotine exposure during prenatal life may alter central and peripheral respiratory chemoreception.

“Rodent studies have indicated that nicotine exposure during prenatal life may alter central and peripheral respiratory chemoreception.46,47”

• cites [46] Cerpa, 2015, The alteration of neonatal raphe neurons by prenatal-perinatal nicotine. Meaning for sudden infant death syndrome, Am J Respir Cell Mol Biol sourcePartly supported

  The Abstract reports that prenatal–perinatal nicotine exposure reduces central respiratory chemoreception in neonatal mice, and the study found a diminished ventilatory response to hypercapnia. Our copy does not establish an effect on peripheral respiratory chemoreception; its mention of reduced responses to hypoxia does not identify a peripheral mechanism. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [47] Mahliere, 2008, Prenatal nicotine alters maturation of breathing and neural circuits regulating respiratory control, Respir Physiol Neurobiol sourceNot checked — no full text of the source

Men with prior in utero smoke exposure had significant reductions in FEV1 and midexpiratory flow.

“Hayatbakhsh and colleagues 51 also found that men with prior in utero smoke exposure had significant reductions in FEV 1 and midexpiratory flow.”

• cites [51] Hayatbakhsh, 2009, Maternal smoking during and after pregnancy and lung function in early adulthood: a prospective study, Thorax sourceSupported

Neonatal mice exposed to nicotine in utero had decreased ventilation and a reduced response to hypercarbia when exposed to 100% nitrogen for 20 seconds and 10% CO2 for 20 minutes.

“Another study reported that neonatal mice exposed to nicotine in utero had decreased ventilation and a reduced response to hypercarbia when exposed to 100% nitrogen for 20 seconds and 10% CO 2 for 20 minutes.49”

• cites [49] Eugenin, 2008, Prenatal to early postnatal nicotine exposure impairs central chemoreception and modifies breathing pattern in mouse neonates: a probable link to sudden infant death syndrome, J Neurosci sourceSupported

Other nicotinic receptor subtypes expressed in fetal lung are not upregulated by nicotine.

“They also found that nicotine increased expression of a7 receptors in airway cartilage and vessels of fetal lung and that other nicotinic receptor subtypes, although expressed in fetal lung, were not upregulated by nicotine.30”

• cites [30] Sekhon, 1999, Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys, J Clin Invest sourceSupported

Nicotine increases expression of a7 receptors in airway cartilage and vessels of fetal lung.

“They also found that nicotine increased expression of a7 receptors in airway cartilage and vessels of fetal lung and that other nicotinic receptor subtypes, although expressed in fetal lung, were not upregulated by nicotine.30”

• cites [30] Sekhon, 1999, Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys, J Clin Invest sourceSupported

Nicotine exposure in pregnant rhesus monkeys causes alveolar hypoplasia in offspring.

“Sekhon and colleagues 30 implanted nicotine pumps in pregnant rhesus monkeys and found reduced total body weight and alveolar hypoplasia in the offspring.”

• cites [30] Sekhon, 1999, Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys, J Clin Invest sourceSupported

In fetal and infant sudden death cases, higher incidence of a7 nAChR immunostaining in lung is associated with maternal smoking.

“A recent study of lung tissue from fetal and infant sudden death cases found a higher incidence of a7 nAChR immunostaining in lung associated with maternal smoking, and maternal smoking was linked to”

• cites [41] Lavezzi, 2014, Possible role of the alpha7 nicotinic receptors in mediating nicotine's effect on developing lung - implications in unexplained human perinatal death, BMC Pulm Med sourceSupported

Nicotine exposure causes downregulation of n-Myc expression in nonhuman primate embryonic stem cells.

“In their study, exposure of nicotine caused downregulation of n-Myc expression and differentiation of nonhuman primate embryonic stem cells into fibroblasts, demonstrating that exposure to nicotine during embryogenesis can affect embryonic stem cell differentiation.”

• cites [29] Ben-Yehudah, 2013, Nicotine exposure during differentiation causes inhibition of N-myc expression, Respir Res sourceSupported

Nicotine exposure in pregnant rhesus monkeys reduces total body weight in offspring.

“Sekhon and colleagues 30 implanted nicotine pumps in pregnant rhesus monkeys and found reduced total body weight and alveolar hypoplasia in the offspring.”

• cites [30] Sekhon, 1999, Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys, J Clin Invest sourceSupported

Since the 1980s, studies have demonstrated increased risk for lower respiratory tract infections in infants exposed to maternal smoke.

“Since the 1980s, studies have demonstrated increased risk for lower respiratory tract infections in infants exposed to maternal smoke.56,57”

• cites [56] Fergusson, 1980, Parental smoking and respiratory illness in infancy, Arch Dis Child sourceSupported
• cites [57] Taylor, 1987, Maternal smoking during pregnancy and lower respiratory tract illness in early life, Arch Dis Child sourceSupported

Exposure to nicotine during embryogenesis can affect embryonic stem cell differentiation.

“In their study, exposure of nicotine caused downregulation of n-Myc expression and differentiation of nonhuman primate embryonic stem cells into fibroblasts, demonstrating that exposure to nicotine during embryogenesis can affect embryonic stem cell differentiation.”

• cites [29] Ben-Yehudah, 2013, Nicotine exposure during differentiation causes inhibition of N-myc expression, Respir Res sourceSupported

Maternal smoking was reported in 38.6% of infants dying of SIDS in a 2012 study.

“A 2012 study found that maternal smoking was reported in 38.6% of infants dying of SIDS.44”

• cites [44] Trachtenberg, 2012, Risk factor changes for sudden infant death syndrome after initiation of Back-to-Sleep campaign, Pediatrics sourcePartly supported

  The Results table reports maternal smoking in 78 SIDS cases (38.6%) during the 1996–2008 Back-to-Sleep era. The claim omits that this percentage applies to that period, rather than to all SIDS cases in the study. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Tissue-specific epigenetic patterns may lead to differing functional consequences.

“Significant variability in methylation patterns between cord blood and placental and saliva samples suggests tissue-specific epigenetic patterns, 79 which may lead to differing functional consequences.80”

• cites [80] Lokk, 2014, DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns, Genome Biol sourceSupported

Epigenetic differences in global DNA methylation have been found between smokers and nonsmokers.

“Subsequently, epigenetic differences in global DNA methylation have been found between smokers and nonsmokers.70,71”

• cites [70] Breitling, 2011, Tobacco-smoking-related differential DNA methylation: 27K discovery and replication, Am J Hum Genet sourceNot checked — no full text of the source
• cites [71] Zeilinger, 2013, Tobacco smoking leads to extensive genome-wide changes in DNA methylation, PLoS One sourcePartly supported

  The Results and Discussion section reports 972 differentially methylated CpG sites across the genome, including 187 replicated sites, when comparing current with never smokers. That supports widespread site-specific differences, but the paper does not report a difference in global DNA methylation as an overall measure. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Decreased monocyte interferon production at birth is correlated with increased risk of early life infection.

“Sumino and colleagues 62 correlated decreased monocyte interferon production at birth with increased risk of early life infection.”

• cites [62] Sumino, 2012, Antiviral IFN-gamma responses of monocytes at birth predict respiratory tract illness in the first year of life, J Allergy Clin Immunol sourcePartly supported

  The Discussion reports that lower RSV-induced IFNG mRNA in cord-blood monocytes at birth was associated with more respiratory tract illness during the first year of life in infants at high risk for asthma and allergic disease. The claim broadens this to early-life infection generally; the Discussion says the response was not linked to some other types of infection. The measured response was IFNG mRNA, rather than interferon protein production. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Placental studies have demonstrated changes in global and gene-specific methylation.

“Placental studies also have demonstrated changes in global and gene-specific methylation.78”

• cites [78] Maccani, 2015, Altered placental DNA methylation patterns associated with maternal smoking: current perspectives, Adv Genomics Genet sourcePartly supported

  The Conclusion and future directions reports gene-specific placental methylation changes associated with maternal smoking, but says epigenome-wide changes may occur only “perhaps, to a lesser degree.” Genetic pathways associated with MCSDP reports changes in repetitive-element methylation associated with epigenome-wide patterns. These passages support gene-specific changes but are more cautious than the claim that global changes have been demonstrated. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Cord blood studies have implicated smoking-induced methylation changes in multiple specific genes, including CYP1A1, GF1, FOXP3, and AHRR.

“Cord blood studies have implicated smokinginduced methylation changes in multiple specific genes, including CYP1A1, GF1, FOXP3, and AHRR, [72][73][74] which play a role in detoxification and immune regulation and, therefore, may contribute to childhood lung disease.”

• cites [72] Suter, 2010, In utero tobacco exposure epigenetically modifies placental CYP1A1 expression, Metabolism sourcePartly supported

  The Discussion reports smoking-associated hypomethylation of CYP1A1 in placenta, supporting that gene’s inclusion. But it explicitly says CYP1A1 and its promoter were not assayed in fetal blood; this paper does not establish cord-blood methylation changes in CYP1A1 or the other listed genes. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [73] Hinz, 2012, Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year, Allergy sourceNot checked — no full text of the source
• cites [74] Joubert, 2012, 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy, Environ Health Perspect sourcePartly supported

  The Results and Discussion report smoking-associated cord-blood methylation differences in CYP1A1, AHRR, and GFI1—the likely intended gene behind “GF1.” The paper does not report a corresponding finding for FOXP3, so it does not support the full gene list attributed to it. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

A separate longitudinal study detected persistent AHRR methylation changes at 7 years of age.

“Novakovic and colleagues 76 recently demonstrated persistent AHRR hypomethylation in blood monocytes at 1 year of age, and a separate longitudinal study detected persistent changes at 7 years of age.72,77”

• cites [72] Suter, 2010, In utero tobacco exposure epigenetically modifies placental CYP1A1 expression, Metabolism sourceCould not verify

  The Results and Discussion describe CYP1A1 methylation in placenta and speculate that it may provide a memory of fetal tobacco exposure. Our copy does not report AHRR methylation or a longitudinal finding at age 7 (searched for AHRR and seven-year follow-up); no page numbers are available in the copy. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [77] Richmond, 2015, Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC), Hum Mol Genet sourceSupported

These epigenetic changes in AHRR methylation persist well into postnatal life.

“These epigenetic changes in AHRR methylation persist well into postnatal life.”

• cites [76] Novakovic, 2014, Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy, Epigenetics sourceSupported
• cites [72] Suter, 2010, In utero tobacco exposure epigenetically modifies placental CYP1A1 expression, Metabolism sourceCould not verify

  The Introduction reports altered CYP1A1 methylation in placentas, while the Discussion describes persistence of tobacco-related epigenetic changes as a possibility, not an observed postnatal result. Searches for AHRR and postnatal persistence found no passage establishing that AHRR methylation changes persist after birth. Page numbers were not available in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [77] Richmond, 2015, Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC), Hum Mol Genet sourceSupported

Decreased expression of interferon-inducible GTPases and type 1 interferon response pathway genes induced by viral double-stranded RNA were found in the lungs of neonatal mice exposed to SHS.

“In addition, decreased expression of interferon-inducible GTPases and type 1 interferon response pathway genes induced by viral double-stranded RNA were found in the lungs of neonatal mice exposed to SHS. 33”

• cites [33] McGrath-Morrow, 2008, Impaired lung homeostasis in neonatal mice exposed to cigarette smoke, Am J Respir Cell Mol Biol sourceSupported

These neonatal changes in AHRR methylation correlated with maternal levels of cotinine.

“These neonatal changes correlated with maternal levels of cotinine.74”

• cites [74] Joubert, 2012, 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy, Environ Health Perspect sourceSupported

Neonatal mice exposed to nicotine in utero had enhanced M2 phenotype in their alveolar macrophages.

“Neonatal mice exposed to nicotine in utero had enhanced M2 phenotype in their alveolar macrophages.65”

• cites [65] Wongtrakool, 2012, In utero nicotine exposure promotes M2 activation in neonatal mouse alveolar macrophages, Pediatr Res sourceSupported

In a 2013 study comparing neonates born to smoking and nonsmoking mothers, there was no difference in lymphocyte subsets between the two groups.

“Indeed, in a 2013 study comparing neonates born to smoking and nonsmoking mothers, Almanzar and colleagues 64 found no difference in lymphocyte subsets between the two groups.”

• cites [64] Almanzar, 2013, Maternal cigarette smoking and its effect on neonatal lymphocyte subpopulations and replication, BMC Pediatr sourceSupported

Novakovic and colleagues demonstrated persistent AHRR hypomethylation in blood monocytes at 1 year of age.

“Novakovic and colleagues 76 recently demonstrated persistent AHRR hypomethylation in blood monocytes at 1 year of age, and a separate longitudinal study detected persistent changes at 7 years of age.72,77”

• cites [76] Novakovic, 2014, Postnatal stability, tissue, and time specific effects of AHRR methylation change in response to maternal smoking in pregnancy, Epigenetics sourcePartly supported

  The section “Maternal smoking-induced hypomethylation of AHRR is maintained at 18 mo” reports that the methylation difference associated with maternal smoking persisted after birth. It measured peripheral blood mononuclear cells at 18 months, not isolated monocytes at 1 year of age. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Subsequent research has demonstrated increased airway resistance and decreased lung function after in utero smoke exposure in children with GSTTI and GSTP1 alleles.

“Subsequent research has demonstrated physiologic changes, including increased airway resistance and decreased lung function after in utero smoke exposure in children with GSTTI and GSTP1 alleles.86,88”

• cites [86] Murdzoska, 2010, In utero smoke exposure and role of maternal and infant glutathione s-transferase genes on airway responsiveness and lung function in infancy, Am J Respir Crit Care Med sourceNot checked — no full text of the source
• cites [88] Kabesch, 2004, Glutathione S transferase deficiency and passive smoking increase childhood asthma, Thorax sourcePartly supported

  The Results (page not provided) report decreased lung-function measurements in children with a GSTT1 null genotype exposed to smoke in utero. The paper studied GSTM1 and GSTT1, not GSTP1, and the cited passages do not report increased airway resistance. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

• AssumptionRests on an assumption: Glutathione S-transferase enzymes play a role in metabolizing tobacco products and reactive oxygen species.

Nicotine caused fibroblast differentiation in nonhuman embryonic stem cells.

“| Y N-myc expression | Nicotine caused fibroblast differentiation in nonhuman | 29 |”

• cites [29] Ben-Yehudah, 2013, Nicotine exposure during differentiation causes inhibition of N-myc expression, Respir Res sourcePartly supported

  The Methods (In Vitro differentiation; page unavailable) say that a directed protocol differentiated nonhuman primate embryonic stem cells into fibroblasts, with nicotine added to one experimental group. The Discussion reports altered gene expression in cells differentiated in nicotine’s presence, but the paper does not show that nicotine itself caused fibroblast differentiation. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

The grandmaternal effect on childhood asthma risk was unable to be replicated using data from the Avon Longitudinal Study of Parents and Children.

“In this nested case control study, grandmaternal smoking was associated with a 2.1 OR risk of developing childhood asthma; however, this effect was unable to be replicated using data from the Avon Longitudinal Study of Parents and Children.83”

• cites [83] Miller, 2014, Do grandmaternal smoking patterns influence the etiology of childhood asthma?, Chest sourceSupported

The Norwegian Mother and Child Cohort Study found a strong association between grandmaternal smoking during pregnancy and childhood asthma.

“The Norwegian Mother and Child Cohort Study also found a strong association between grandmaternal smoking during pregnancy and childhood asthma.84”

• cites [84] Magnus, 2015, Grandmother's smoking when pregnant with the mother and asthma in the grandchild: the Norwegian Mother and Child Cohort Study, Thorax sourcePartly supported

  The Results report an association between the grandmother’s smoking while pregnant with the mother and asthma in the grandchild, but explicitly call it “modest” (adjusted risk ratios 1.15–1.21). Describing the association as strong overstates the finding. (LLM, conf=0.91)

  Experimental — accuracy not yet measured

The lungs of mice exposed to nicotine-containing e-cigarette aerosols had decreased total glutathione.

“Furthermore, they reported that the lungs of mice exposed to nicotine-containing e-cigarette aerosols had decreased total glutathione.”

• cites [95] Lerner, 2015, Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung, PLoS One sourceSupported

One of the first articles looking at the effects of in utero smoke exposure on fetal lung-specific methylation found changes in methylation of DPP10, a gene associated with asthma.

“One of the first articles looking at the effects of in utero smoke exposure on fetal lung-specific methylation found changes in methylation of DPP10, a gene associated with asthma.22”

• cites [22] Chhabra, 2014, Fetal lung and placental methylation is associated with in utero nicotine exposure, Epigenetics sourceSupported

Prenatal nicotine exposure caused α7 nAChRs in airway, cartilage, and vessels in rhesus monkeys.

“| [ a7 nAChRs | Prenatal nicotine exposure caused [ a7 nAChRs in airway, | 30 |”

• cites [30] Sekhon, 1999, Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys, J Clin Invest sourcePartly supported

  The Nicotinic receptor immunohistochemistry section reports that prenatal nicotine markedly increased α7 staining in airway epithelial cells, cartilaginous airway wall regions, and blood vessel walls. Figure 2 (p. 640) also shows α7 staining in control fetuses, so the paper supports increased expression, not the claim that nicotine caused the receptors to appear. It does not establish increased expression in cartilage itself. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Exposure to e-cigarette aerosols may increase oxidative stress and inflammation in the lung.

“Taken together, these findings indicate that exposure to e-cigarette aerosols may increase oxidative stress and inflammation in the lung.95”

• cites [95] Lerner, 2015, Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung, PLoS One sourceSupported

The first genomewide interaction study of early life tobacco exposure and asthma, published in 2014, identified novel polymorphisms on chromosomes 6 and 18.

“The first genomewide interaction study of early life tobacco exposure and asthma was published in 2014 and identified novel polymorphisms on chromosomes 6 and 18. 85”

• cites [85] Scholtens, 2014, Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure, J Allergy Clin Immunol sourceSupported

Prenatal smoke exposure caused Th1 and Th2 changes in mice after Aspergillus sensitization.

“| Y Interferon-g | Prenatal smoke exposure caused Th1 and Th2 changes in | 31 |”

• cites [31] Singh, 2011, Prenatal secondhand cigarette smoke promotes Th2 polarization and impairs goblet cell differentiation and airway mucus formation, J Immunol sourceSupported

Additional candidate genes CYP1A1, ADAM33, and TNF have been suggested to modify the risk of subsequent asthma.

“Additional candidate genes, CYP1A1, ADAM33, and TNF, have been suggested to modify the risk of subsequent asthma.85,90,91”

• cites [85] Scholtens, 2014, Novel childhood asthma genes interact with in utero and early-life tobacco smoke exposure, J Allergy Clin Immunol sourcePartly supported

  In the paper’s discussion (page not available in our copy), TNF and ADAM33 are described as genes previously reported to interact with tobacco-smoke exposure in asthma development. CYP1A1 is not mentioned, and TNF and ADAM33 were not among this study’s most significant hits. The source therefore supports the suggestion for two of the three named genes, not all three. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [90] Chen, 2011, Maternal smoking during pregnancy, polymorphic CYP1A1 and GSTM1, and lung-function measures in urban family children, Environ Res sourceNot checked — no full text of the source
• cites [91] Reijmerink, 2009, Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness, Allergy sourceNot checked — no full text of the source

Exposure to nicotine and nonnicotine flavored e-cigarette juices increased levels of the proinflammatory cytokines IL-6 and IL-8 in human epithelial cells and fibroblasts.

“Lerner and colleagues 95 reported increased levels of the proinflammatory cytokines, IL-6, and IL-8 in human epithelial cells and fibroblasts exposed to nicotine and nonnicotine flavored e-cigarette juices.”

• cites [95] Lerner, 2015, Vapors produced by electronic cigarettes and e-juices with flavorings induce toxicity, oxidative stress, and inflammatory response in lung epithelial cells and in mouse lung, PLoS One sourcePartly supported

  The Results report increased IL-6 and IL-8 secretion in human H292 epithelial cells exposed to tobacco-flavored e-cigarette aerosols. In the lung-fibroblast Results, only cinnamon-flavored e-liquid significantly increased IL-8 versus controls; the passage does not report increased IL-6 in fibroblasts, and nicotine-containing tobacco e-liquid did not significantly increase fibroblast IL-8 versus controls. Page numbers were not provided in our copy's passages. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Prenatal and postnatal tobacco smoke and nicotine exposure can impair lung development.

“Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood.”

• AssumptionRests on an assumption: Observed associations between tobacco smoke exposure and childhood respiratory outcomes reflect causal effects of tobacco smoke or nicotine.
• AssumptionRests on an assumption: Nicotine is a key mediator of the adverse effects of tobacco smoke on lung development.

Exposed neonates are at increased risk for altered central and peripheral respiratory chemoreception.

“Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood.”

Nicotine is concentrated in the breast milk of mothers who smoke.

“Nicotine has also been shown to be concentrated in the breast milk of mothers who smoke.13,14”

• cites [13] Schulte-Hobein, 1992, Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant's urine, Acta Paediatr sourceNot checked — no full text of the source
• cites [14] Schwartz-Bickenbach, 1987, Smoking and passive smoking during pregnancy and early infancy: effects on birth weight, lactation period, and cotinine concentrations in mother's milk and infant's urine, Toxicol Lett sourceNot checked — no full text of the source

Cotinine levels in neonates exposed to in utero tobacco smoke have been reported to be similar to that of active smoking adults.

“Indeed, cotinine levels in neonates exposed to in utero tobacco smoke have been reported to be similar to that of active smoking adults.24,25”

• cites [24] Ivorra, 2014, High cotinine levels are persistent during the first days of life in newborn second hand smokers, Drug Alcohol Depend sourceNot checked — no full text of the source
• cites [25] Chazeron, 2008, GC-MS determined cotinine in an epidemiological study on smoking status at delivery, Pulm Pharmacol Ther sourceNot checked — no full text of the source

Postnatal exposure of children to SHS continues to be widespread.

“Postnatal exposure of children to SHS continues to be widespread.”

• cites [27] Oberg, 2011, Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries, Lancet sourceNot checked — no full text of the source

Nicotine crosses the placenta in utero.

“Nicotine, the primary addictive substance in tobacco smoke, has been shown to cross the placenta in utero as evidenced by high levels of cotinine, a nicotine metabolite, in the amniotic fluid of pregnant smokers and in blood spots from neonates exposed in utero.11,12”

• cites [11] Luck, 1985, Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers, Dev Pharmacol Ther sourceNot checked — no full text of the source
• cites [12] Jauniaux, 1999, Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy, Obstet Gynecol sourceNot checked — no full text of the source

Infants and young children may be at highest risk for toxicity from secondhand and thirdhand smoke exposure.

“Furthermore, infants and young children may be at highest risk for toxicity from secondhand and thirdhand smoke exposure because they tend to spend more time indoors, have faster respiratory rates, have a greater relative body surface area, and have more hand or oral behaviors than do older children.”

Exposed neonates are at increased risk for increased asthma symptoms throughout childhood.

“Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood.”

Maternal smoking was associated with a longer length of stay in the neonatal intensive care unit.

“Analysis from the Pregnancy Risk Assessment Monitoring System for 2001 and 2002 revealed that maternal smoking was associated with a longer length of stay in the neonatal intensive care unit, with an estimated smoking-attributable cost of $122 million annually in the United States.26”

• cites [26] Adams, 2011, Infant delivery costs related to maternal smoking: an update, Nicotine Tob Res sourceNot checked — no full text of the source

Prenatal and postnatal tobacco smoke and nicotine exposure can increase the prevalence of wheezing during childhood.

“Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood.”

• AssumptionRests on an assumption: Observed associations between tobacco smoke exposure and childhood respiratory outcomes reflect causal effects of tobacco smoke or nicotine.
• AssumptionRests on an assumption: Nicotine is a key mediator of the adverse effects of tobacco smoke on lung development.

Exposed neonates are at increased risk for diminished lung function.

“Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood.”

Tobacco smoke exposure during prenatal and postnatal lung development is associated with an increase in respiratory morbidities during childhood.

“Tobacco smoke exposure during prenatal and postnatal lung development is associated with an increase in respiratory morbidities during childhood.”

• AssumptionRests on an assumption: Observed associations between tobacco smoke exposure and childhood respiratory outcomes reflect causal effects of tobacco smoke or nicotine.

Prenatal and postnatal tobacco smoke and nicotine exposure can alter the immune response to viral infections.

“Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood.”

• AssumptionRests on an assumption: Observed associations between tobacco smoke exposure and childhood respiratory outcomes reflect causal effects of tobacco smoke or nicotine.
• AssumptionRests on an assumption: Nicotine is a key mediator of the adverse effects of tobacco smoke on lung development.

The risk of COPD in adult life may be influenced by SHS during childhood.

“This finding suggests that that the risk of COPD in adult life may be influenced by SHS during childhood because children exposed to SHS are more likely to have a history of lower respiratory tract infections.”

Thirdhand smoke may have enhanced toxicity compared with mainstream smoke.

“Because of oxidation and breakdown processes, thirdhand smoke may have enhanced toxicity compared with mainstream smoke.”

Aberrant growth and inflammation of the small airways from tobacco exposure during in utero and early postnatal life may, in part, account for the observed symptoms and outcomes in these studies.

“Aberrant growth and inflammation of the small airways from tobacco exposure during in utero and early postnatal life may, in part, account for the observed symptoms and outcomes in these studies.”

nAChR expression in the brain and lung during early fetal life represents a potential mechanism for the effects of nicotine on development.

“nAChRs have been shown to be expressed in the brain and lung during early fetal life, thus representing a potential mechanism for the effects of nicotine on development.”

• AssumptionRests on an assumption: Nicotine is a key mediator of the adverse effects of tobacco smoke on lung development.

Human lung development spans both prenatal and postnatal life.

“Human lung development spans both prenatal and postnatal life 1 and can be adversely affected by exposure to tobacco smoke and nicotine during both of these periods.”

• cites [1] Smith, 2010, Normal development of the lung and premature birth, Paediatr Respir Rev sourceNot checked — no full text of the source

Neonatal rats exposed to prenatal cigarette smoke had prolonged gasping following a hyperthermic or hypoxic exposure.

“A study in neonatal rats found that pups exposed to prenatal cigarette smoke had prolonged gasping following a hyperthermic or hypoxic exposure.48”

• cites [48] Pendlebury, 2008, Respiratory control in neonatal rats exposed to prenatal cigarette smoke, Am J Respir Crit Care Med sourceNot checked — no full text of the source

nAChRs are expressed in the brain and lung during early fetal life.

“nAChRs have been shown to be expressed in the brain and lung during early fetal life, thus representing a potential mechanism for the effects of nicotine on development.”

If a causal association is assumed, one-third of SIDS deaths may have been avoided if the infant had not been exposed to smoke in utero.

“Mitchell and Milerad 45 reported that the pooled relative risk of SIDS associated with maternal smoking was 2.86; furthermore, if a causal association was assumed, one-third of SIDS deaths may have been avoided if the infant had not been exposed to smoke in utero.”

• cites [45] Mitchell, 2006, Smoking and the sudden infant death syndrome, Rev Environ Health sourceNot checked — no full text of the source

• AssumptionRests on an assumption: Observed associations between tobacco smoke exposure and childhood respiratory outcomes reflect causal effects of tobacco smoke or nicotine.

Children of mothers who smoked, validated by cotinine levels, were more likely to have increased airway resistance and higher fraction of exhaled nitric oxide levels than nonexposed children.

“A Finnish study that examined young children with a history of multitrigger wheezing found that children of mothers who smoked, validated by cotinine levels, were more likely to have increased airway resistance and higher fraction of exhaled nitric oxide levels than were nonexposed children.17”

• cites [17] Kalliola, 2013, Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze, J Allergy Clin Immunol sourceNot checked — no full text of the source

Human bronchial and endothelial cells express a3/b4 and a7 nAChRs.

“Human bronchial and endothelial cells have been reported to express a3/b4 and a7 nAChRs.35”

• cites [35] Wang, 2001, Human bronchial epithelial and endothelial cells express alpha7 nicotinic acetylcholine receptors, Mol Pharmacol sourceNot checked — no full text of the source

At 4 years of age, children with postnatal exposure alone did not have increased wheezing.

“In 3-yearold children within the Generation R cohort, there was an increased risk of wheezing with any prenatal or postnatal tobacco smoke exposure, but at 4 years of age, those with postnatal exposure alone did not have increased wheezing.5,50”

• cites [5] den Dekker, 2015, Tobacco smoke exposure, airway resistance, and asthma in school-age children: the Generation R Study, Chest sourceNot checked — no full text of the source
• cites [50] Duijts, 2012, Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study, Chest sourceNot checked — no full text of the source

Tobacco smoke exposure is linked to an increased risk of sudden infant death syndrome (SIDS).

“Tobacco smoke exposure has been linked to an increased risk of sudden infant death syndrome (SIDS).”

Vitamin C given to pregnant rhesus monkeys improves lung function in nicotine-exposed offspring.

“Proskocil and colleagues 42 reported that vitamin C, when given to pregnant rhesus monkeys, improved lung function in nicotine-exposed offspring.”

• cites [42] Proskocil, 2005, Vitamin C prevents the effects of prenatal nicotine on pulmonary function in newborn monkeys, Am J Respir Crit Care Med sourceNot checked — no full text of the source

In 3-year-old children within the Generation R cohort, there was an increased risk of wheezing with any prenatal or postnatal tobacco smoke exposure.

“In 3-yearold children within the Generation R cohort, there was an increased risk of wheezing with any prenatal or postnatal tobacco smoke exposure, but at 4 years of age, those with postnatal exposure alone did not have increased wheezing.5,50”

• cites [5] den Dekker, 2015, Tobacco smoke exposure, airway resistance, and asthma in school-age children: the Generation R Study, Chest sourceNot checked — no full text of the source
• cites [50] Duijts, 2012, Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study, Chest sourceNot checked — no full text of the source

The pooled relative risk of SIDS associated with maternal smoking is 2.86.

“Mitchell and Milerad 45 reported that the pooled relative risk of SIDS associated with maternal smoking was 2.86; furthermore, if a causal association was assumed, one-third of SIDS deaths may have been avoided if the infant had not been exposed to smoke in utero.”

• cites [45] Mitchell, 2006, Smoking and the sudden infant death syndrome, Rev Environ Health sourceNot checked — no full text of the source

Cord blood from neonates exposed to smoke in utero had increased levels of IL-13 after antigen challenge.

“Noakes and colleagues 63 found that cord blood from neonates exposed to smoke in utero had increased levels of IL-13 after antigen challenge.”

• cites [63] Noakes, 2003, Maternal smoking in pregnancy alters neonatal cytokine responses, Allergy sourceNot checked — no full text of the source

Continued environmental tobacco smoke exposure suppresses interferon-g levels through 11 years of age.

“Prenatal exposure to tobacco smoke can cause decreased levels of cord blood interferon-g, and continued environmental tobacco smoke exposure has been shown to suppress interferon-g levels through 11 years of age.59,61”

• cites [59] Macaubas, 2003, Association between antenatal cytokine production and the development of atopy and asthma at age 6 years, Lancet sourceNot checked — no full text of the source
• cites [61] Tebow, 2008, Effects of parental smoking on interferon gamma production in children, Pediatrics sourceNot checked — no full text of the source

After birth, the immune response normally shifts toward a Th1 immune response.

“After birth, the immune response normally shifts toward a Th1 immune response.”

Significant variability in methylation patterns between cord blood and placental and saliva samples suggests tissue-specific epigenetic patterns.

“Significant variability in methylation patterns between cord blood and placental and saliva samples suggests tissue-specific epigenetic patterns, 79 which may lead to differing functional consequences.80”

• cites [79] Armstrong, 2014, Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research, FASEB J sourceNot checked — no full text of the source

Fetal T-helper cells exhibit a predominantly antiinflammatory Th2 response.

“Consequently, fetal T-helper cells exhibit a predominantly antiinflammatory Th2 response.60”

• cites [60] Ygberg, 2012, The developing immune system - from foetus to toddler, Acta Paediatr sourceNot checked — no full text of the source

Prenatal exposure to tobacco smoke can cause decreased levels of cord blood interferon-g.

“Prenatal exposure to tobacco smoke can cause decreased levels of cord blood interferon-g, and continued environmental tobacco smoke exposure has been shown to suppress interferon-g levels through 11 years of age.59,61”

• cites [59] Macaubas, 2003, Association between antenatal cytokine production and the development of atopy and asthma at age 6 years, Lancet sourceNot checked — no full text of the source
• cites [61] Tebow, 2008, Effects of parental smoking on interferon gamma production in children, Pediatrics sourceNot checked — no full text of the source

In utero smoke increases the levels of cytokines associated with Th2 immune profiles.

“In addition to decreasing interferon-g levels, in utero smoke increases the levels of cytokines associated with Th2 immune profiles.”

Changes in AHRR methylation may contribute to altered detoxification function and subsequent disease development.

“Changes in AHRR methylation may contribute to altered detoxification function and subsequent disease development.”

Epigenetic modification of gene expression and phenotype plays an important role in fetal development.

“Epigenetic modification of gene expression and phenotype plays an important role in fetal development; furthermore, the epigenome that develops in utero and in early life persists throughout life and is heritable.67”

• cites [67] Reik, 2007, Stability and flexibility of epigenetic gene regulation in mammalian development, Nature sourceNot checked — no full text of the source

Studies of human cord blood have shown decreased methylation in AHRR loci in neonates similar to immune cell methylation patterns in adult smokers.

“Studies of human cord blood have shown decreased methylation in AHRR loci in neonates similar to immune cell methylation patterns in adult smokers.”

Prenatal maternal smoking may carry a higher risk of subsequent infection.

“Prenatal maternal smoking may carry a higher risk of subsequent infection, suggesting a developmental mechanism for the increased vulnerability, 58,59 but the underlying mechanisms that account for this increased infection risk are not fully understood.”

• cites [58] Haberg, 2007, Effects of pre- and postnatal exposure to parental smoking on early childhood respiratory health, Am J Epidemiol sourceNot checked — no full text of the source
• cites [59] Macaubas, 2003, Association between antenatal cytokine production and the development of atopy and asthma at age 6 years, Lancet sourceNot checked — no full text of the source

Grandmaternal smoking was associated with a 2.1 OR risk of developing childhood asthma in a nested case control study.

“In this nested case control study, grandmaternal smoking was associated with a 2.1 OR risk of developing childhood asthma; however, this effect was unable to be replicated using data from the Avon Longitudinal Study of Parents and Children.83”

• cites [82] Li, 2005, Maternal and grandmaternal smoking patterns are associated with early childhood asthma, ChestNot matched

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

Electronic nicotine delivery systems may cause different physiologic or pathologic changes in the developing lung compared with those seen with nicotine replacement therapy.

“This in turn may cause different physiologic or pathologic changes in the developing lung compared with those seen with nicotine replacement therapy.”

• AssumptionRests on an assumption: Electronic nicotine delivery systems have the capacity to deliver a high level burst of nicotine.

The epigenetic effects of tobacco smoke may extend beyond direct effects on gene expression to transgenerational changes in lung development.

“Intriguingly, the epigenetic effects of tobacco smoke may extend beyond direct effects on gene expression to transgenerational changes in lung development.”

Maternal smoking increased the risk of wheezing in children who had a GSTP1 AA genotype.

“Wu and colleagues 89 reported in a population-based birth cohort that maternal smoking increased the risk of wheezing in children who had a GSTP1 AA genotype; however, the effect of maternal smoking on wheeze diminished with age.”

• cites [89] Wu, 2013, Interaction between glutathione S-transferase variants, maternal smoking and childhood wheezing changes with age, Pediatr Allergy Immunol sourceNot checked — no full text of the source

The effect of maternal smoking on wheeze diminished with age in children who had a GSTP1 AA genotype.

“Wu and colleagues 89 reported in a population-based birth cohort that maternal smoking increased the risk of wheezing in children who had a GSTP1 AA genotype; however, the effect of maternal smoking on wheeze diminished with age.”

• cites [89] Wu, 2013, Interaction between glutathione S-transferase variants, maternal smoking and childhood wheezing changes with age, Pediatr Allergy Immunol sourceNot checked — no full text of the source

Non-e-cigarette users exposed to e-cigarette aerosols in the environment had similar cotinine levels as those exposed to secondhand smoke from tobacco-containing cigarettes.

“One study reported that non-e-cigarette users exposed to e-cigarette aerosols in the environment had similar cotinine levels as those exposed to SHS from tobacco-containing cigarettes.92”

• cites [92] Ballbe, 2014, Cigarettes vs. e-cigarettes: passive exposure at home measured by means of airborne marker and biomarkers, Environ Res sourceNot checked — no full text of the source

Linkage studies have implicated chromosomal regions 1p, 1q, 5q, and 17p as modifying asthma risk after early life smoke exposure.

“Linkage studies have also implicated chromosomal regions 1p, 1q, 5q, and 17p as modifying asthma risk after early life smoke exposure.”

Polymorphisms have been implicated in asthma pathogenesis.

“Polymorphisms have been implicated in asthma pathogenesis.86”

• cites [86] Murdzoska, 2010, In utero smoke exposure and role of maternal and infant glutathione s-transferase genes on airway responsiveness and lung function in infancy, Am J Respir Crit Care Med sourceNot checked — no full text of the source

The nicotine component of e-cigarette aerosols may have developmental consequences similar to those of other forms of nicotine delivery.

“Although data are limited regarding the pulmonary effects of e-cigarette aerosols on fetal development, the nicotine component of these aerosols may have developmental consequences similar to those of other forms of nicotine delivery.”