Parental smoking and respiratory outcomes in young childhood cancer survivors

1 INTRODUCTION

Childhood cancer survivors (CCS) are at increased risk of pulmonary late effects because of their cancer treatment.¹ Chemotherapy, radiotherapy, and surgery involving the chest and hematopoietic stem cell transplantation may affect lung function and lead to symptoms like chronic cough and exercise-induced shortness of breath.^{2, 3} Cumulative incidence of adverse pulmonary outcomes continues to increase years after completing cancer treatment.⁴ This indicates continuing susceptibility of survivors’ lungs to initiation and exacerbation of pulmonary diseases. Cancer therapies may also result in delayed immune reconstitution, leaving patients vulnerable to infections well beyond the conclusion of their treatment.^{5, 6} Consequently, infectious complications, such as upper respiratory tract infections (URTI) including sinusitis and otitis media, remain an important cause of late morbidity among survivors, impacting their health and increasing hospitalization rates.^{6, 7}

Even among otherwise healthy individuals, environmental tobacco smoke is a risk factor for respiratory symptoms and infections. Children exposed to parental tobacco smoke have increased susceptibility to recurrent otitis media, asthma, cough, wheeze, and lower respiratory illnesses.⁸ Globally, nearly 40% of children are exposed to tobacco smoke.⁹ In Switzerland, almost one-third of children (31%) grow up in homes where a parent smokes.¹⁰ Parental smoking may have persistent effects on respiratory systems of children, with potential consequences such as impaired lung function and increased risk of respiratory symptoms continuing into adulthood.¹¹ For CCS who may already have compromised respiratory health due to cancer treatments, these effects could be particularly concerning.⁴ Therefore, the aims of this study were to examine the prevalence of parental smoking among Swiss CCS aged ≤16 years and to investigate the associations between parental smoking and respiratory outcomes. We hypothesized that CCS exposed to maternal or paternal smoking would be more likely to experience respiratory outcomes, including symptoms and diseases, compared with those not exposed to parental smoking.

2 METHODS

3 RESULTS

3.1 Characteristics of the study population

Of the 1796 eligible CCS identified through the ChCR, we sent questionnaires to the parents of 1578. Questionnaires were returned by parents in 1070 families (a response rate of 68%). We excluded questionnaires of 33 CCS for whom there were no answers to any of the questions on parental smoking or on respiratory outcomes. The final dataset used for the analysis included 1037 children (Figure 1). Their median age at the time of the study was 12 years (IQR 10−14), the median age at diagnosis was 3 years (IQR 2−5), and the median time since diagnosis was 8 years (IQR 7−10). The most common diagnoses were leukemia (39%), CNS tumors (16%), and neuroblastoma (9%) (Table 1). We compared cancer- and treatment-related characteristics of participants (n = 1037) and nonparticipants (n = 541) and found no significant differences between the groups (Table S1).

TABLE 1. Characteristics of the study population.

N = 1037
Socio-demographic characteristics	n	(%)a
Sex
Male	578	(56)
Female	459	(44)
Median age at study in years (IQR)	12 (10−14)
Swiss language region
German	716	(69)
French	278	(27)
Italian	43	(4)
Migration backgroundb
No	679	(65)
Yes	358	(35)
Living situation
With both parents	889	(86)
With mother only	131	(13)
With father only	12	(1)
Other (children's home, relatives)	5	(<1)

Cancer-related characteristics	n	(%)a
Median age at diagnosis in years (IQR)	3 (2−5)
Median time since diagnosis in years (IQR)	8 (7−10)
Diagnosis (ICCC-3)
Leukemia	408	(39)
Lymphoma	64	(6)
CNS tumor	162	(16)
Neuroblastoma	95	(9)
Retinoblastoma	62	(6)
Renal tumor	83	(8)
Hepatic tumor	15	(2)
Bone tumor	20	(2)
Soft tissue sarcoma	67	(7)
Germ cell tumor	24	(2)
Other tumorc	2	(< 1)
Langerhans cell histiocytosis	35	(3)
Treatment
Chemotherapyd	856	(83)
Radiotherapyd	204	(20)
Surgerye	570	(55)
Hematopoietic stem cell transplantationd	86	(8)
Relapse	118	(11)

• Abbreviations: CNS, central nervous system; ICCC-3, International Classification of Childhood Cancer—Third Edition; IQR, interquartile range.
• ^a Column percentages are given.
• ^b Migration background was considered positive if at least one parent was not of Swiss nationality.
• ^c Other malignant epithelial neoplasms, malignant melanomas, and other or unspecified malignant neoplasms.
• ^d Any chemotherapy, radiotherapy, or hematopoietic stem cell transplantation alone or combined with other treatments.
• ^e Any surgery excluding port-a-cath insertion, alone or combined with other treatments.

Among parents, the median age at the time of the study was 43 years for mothers (IQR 40−47) and 46 years for fathers (IQR 42−50) (Table S2). Secondary education was the most frequently attained educational level of mothers (50%), while tertiary education was the level achieved by the highest proportion of fathers (49%). Almost all survivors lived with both parents (86%) (Table 1). Most fathers (80%), but only 10% of mothers worked full-time (Table S2).

3.4 Associations between parental smoking and respiratory outcomes

In multivariable regression, survivors whose mothers smoked were more likely to have recurrent URTI (odds ratio [OR] 2.1, 95%CI 1.1–3.7) and lower respiratory symptoms (OR 2.0, 95%CI 1.1–3.7) compared with survivors whose mothers did not smoke (Figure 2 and Table S4). Paternal smoking did not show an association with recurrent URTI, asthma, or lower respiratory symptoms.

Older survivors were less likely to have recurrent URTI (OR 0.9, 95%CI 0.8–1.0). With increasing time since diagnosis, survivors were less likely to have recurrent URTI in the univariable regression (OR 0.9, 95%CI 0.8–1.0), but this association was not seen after adjusting in the multivariable regression (OR 0.9, 95%CI 0.8–1.1). Survivors with a history of relapse were more likely to have lower respiratory symptoms in the univariable model (OR 2.1, 95%CI 1.1–3.9), with the trend persisting in the multivariable model (OR 1.9, 95%CI 1.0–3.8). Sex was not associated with any of the respiratory outcomes. Detailed results from univariable logistic regression can be found in Table S5.

4 DISCUSSION

A substantial proportion of young CCS in this nationwide, population-based cohort study are exposed to parents who smoke (31%). We found that maternal smoking was associated with a twofold increased risk of recurrent URTI and lower respiratory symptoms.

Despite the general decline in smoking worldwide over the past two decades,^{15, 16} our study found that a significant proportion of Swiss CCS are exposed to parental smoking, with 18% of mothers and 24% of fathers reported as smokers. A school-based survey on children's respiratory health conducted in the Canton of Zurich between 2013 and 2016 found slightly higher rates, with 20% of mothers and 30% of fathers smoking.¹⁷ Similarly, a 2017 nationwide report on tobacco use by the Swiss Federal Statistical Office indicated that 23% of women and 31% of men aged 15 years and older were daily or occasional smokers.¹⁶ Yet little is known about parental smoking in the families of CCS. A study conducted in the USA found that only 6% of parents of CCS were active smokers compared to 12% of adults in the general population.^{18, 19} The lower prevalence among parents of CCS may be because parents of survivors tend to adopt more health-conscious behaviors.¹⁸ However, it could also be that underreporting is more common in this population.

Our hypothesis that CCS exposed to parental smoking would be more likely to experience respiratory outcomes was partially confirmed, as only maternal smoking was associated with a greater risk of recurrent URTI and lower respiratory symptoms among young (<16 years) CCS. These results are in line with questionnaire-based studies in the general population, which consistently found a stronger impact of maternal smoking on respiratory health than paternal smoking.^20-23 Women are more often primary caregivers and spend more time on average at home with their children.²⁴ In our study, almost all CCS lived with both parents (86%) or only their mothers (13%), and there was a pronounced difference in the employment status of parents, with only 10% of mothers having full-time jobs compared with 80% of fathers. This suggests that survivors may be more susceptible to adverse effects of maternal smoking due to increased exposure to tobacco smoke within the household environment.

Passive smoking contributes to respiratory morbidity in children.⁸ In the late 1990s, a series of comprehensive systematic reviews with meta-analyses revealed consistent evidence for associations between maternal smoking and recurrent otitis media (OR 1.48, 95%CI 1.08–2.04),²⁵ wheeze (OR 1.28, 95%CI 1.19–1.38), and cough (OR 1.40, 95%CI 1.20–1.64).²⁶ A multicountry, questionnaire-based study of 220,407 children (6–7 years) and 350,654 adolescents (13–14 years) found that maternal smoking was associated with wheeze both in children (OR 1.28, 95%CI 1.22–1.34) and adolescents (OR 1.32, 95%CI 1.26–1.37).²¹ Compared to those results, our observations in CCS indicated slightly stronger associations between maternal smoking and recurrent URTI and lower respiratory symptoms. Survivors with a history of relapse were more likely to experience lower respiratory symptoms, perhaps because of more intense and prolonged treatments including chemotherapy, radiation, and hematopoietic stem cell transplantation^{27, 28} Even after accounting for the increased risk from relapse, exposure to maternal smoking was associated with lower respiratory symptoms, highlighting the independent harmful effect of parental smoking for CCS.

In contrast to previous studies conducted among the general population,^{21-23, 29, 30} we found no association between parental smoking and asthma. A systematic review found that children whose parents smoked were more likely to have asthma than children with nonsmoking parents (OR 1.21, 95%CI 1.10–1.34).³¹ The lack of association observed in our study may be due to underreporting or underdiagnosing of asthma. Several studies found that children with parents who smoke were less likely to receive an asthma diagnosis.^{32, 33} This could be because parents who smoke are less likely to seek medical advice regarding mild respiratory symptoms that could be related to smoking in the family.^{32, 33} Another potential explanation is that CCS often receive ongoing medical care focusing on late effects of cancer treatment, which may lead to respiratory symptoms being attributed to these effects rather than asthma. Additionally, immunosuppressive therapies used during cancer treatment can suppress inflammatory responses,^{34, 35} potentially masking asthma symptoms and contributing to underdiagnosis among survivors.

The cross-sectional design of this study does not allow causal conclusions regarding smoking and respiratory outcomes. However, the biological plausibility connecting passive smoking and respiratory conditions is well established.⁸ Passive tobacco smoke has toxic effects on the mucosa, impairs ciliary function and local immune defenses, and results in prolonged inflammation and susceptibility to infections such as otitis media and sinusitis.³⁶ It also contributes to airway thickening and irritation, thereby predisposing children to respiratory symptoms including wheeze and cough.³⁷ Future studies should apply a longitudinal design, which would not only strengthen causal conclusions regarding passive smoking and respiratory health in CCS, but also allow examination of changes in parental smoking behavior over time and associated changes in related health outcomes of CCS.

Self-reported exposures and outcomes may have been subject to recall bias and led to misclassification of some respiratory outcomes in our study. Additionally, we did not collect data on whether parents smoked in proximity to their child, limiting our ability to assess dose–response relationships and exposure to secondhand and thirdhand smoke. To accurately assess survivors’ exposure to passive smoke, future studies should include objective biological markers such as urinary cotinine levels. Due to limited statistical power from the low number of respiratory events, we could not determine associations between parental smoking and respiratory outcomes within different diagnostic and cancer treatment subgroups. Finally, our study did not have a control group. Including a control group in future studies would allow investigation of whether the effects of parental smoking and parental smoking cessation on respiratory health are larger in CCS than in peers without a cancer history.

The strengths of our study include the population-based design and a high response rate, which ensured that the study population is representative of CCSs in Switzerland. We used high-quality clinical information based on medical records from the ChCR and assessed a diverse spectrum of respiratory outcomes.

In conclusion, our study found that exposure to parental smoking is associated with an increased risk of respiratory symptoms and infections among Swiss CCS. Integrating parental smoking cessation strategies into the medical and psychosocial care of childhood cancer patients is essential to create a healthier home environment and promote respiratory health in this vulnerable population. Healthcare providers can support families by addressing caregiver smoking behaviors and providing referrals to specific smoking cessation programs, such as those offered by the Swiss Lung Association (www.lungenliga.ch), the Swiss Cancer League (www.krebsliga.ch), and the national “SmokeFree” campaign (www.stopsmoking.ch), which include effective strategies like counseling sessions and e-health interventions.^{38, 39} The World Health Organization offers valuable guidelines that can further support smoking cessation efforts globally.⁴⁰

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest related to the study.