Father's environment before conception and asthma risk in his children: a multi-generation analysis of the Respiratory Health In Northern Europe study.

Background: Whereas it is generally accepted that maternal environment plays a key role in child health, emerging evidence suggests that paternal environment before conception also impacts child health. We aimed to investigate the association between children's asthma risk and parental smoking and welding exposures prior to conception. Methods: In a longitudinal, multi-country study, parents of 24 168 offspring aged 2-51 years provided information on their life-course smoking habits, occupational exposure to welding and metal fumes, and offspring's asthma before/after age 10 years and hay fever. Logistic regressions investigated the relevant associations controlled for age, study centre, parental characteristics (age, asthma, education) and clustering by family. Results: Non-allergic early-onset asthma (asthma without hay fever, present in 5.8%) was more common in the offspring with fathers who smoked before conception {odds ratio [OR] = 1.68 [95% confidence interval (CI) = 1.18-2.41]}, whereas mothers' smoking before conception did not predict offspring asthma. The risk was highest if father started smoking before age 15 years [3.24 (1.67-6.27)], even if he stopped more than 5 years before conception [2.68 (1.17-6.13)]. Fathers' pre-conception welding was independently associated with non-allergic asthma in his offspring [1.80 (1.29-2.50)]. There was no effect if the father started welding or smoking after birth. The associations were consistent across countries. Conclusions: Environmental exposures in young men appear to influence the respiratory health of their offspring born many years later. Influences during susceptible stages of spermatocyte development might be important and needs further investigation in humans. We hypothesize that protecting young men from harmful exposures may lead to improved respiratory health in future generations.

The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe.

BACKGROUND: There is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar. AIMS: To investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD. METHODS: A postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed. RESULTS: Gum bleeding always/often was significantly associated with ≥ 3 asthma symptoms (OR 2.58, 95% CI 2.10-3.18), asthma (1.62 [1.23-2.14]) and self-reported COPD (2.02 [1.28-3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (≥ 3 symptoms: gum bleeding sometimes 1.42 [1.25-1.60], often/always 2.58 [2.10-3.18]), and there was no heterogeneity between centres (p(heterogeneity) = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (p(interaction) = 0.004). CONCLUSIONS: A consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions.

Respiratory Health in Cleaners in Northern Europe: Is Susceptibility Established in Early Life?

RATIONALE: There is some evidence that maternal smoking increases susceptibility to personal smoking's detrimental effects. One might question whether early life disadvantage might influence susceptibility to occupational exposure. OBJECTIVES: In this cross-sectional study we investigated respiratory symptoms, asthma and self-reported chronic obstructive pulmonary disease (COPD) as related to working as a cleaner in Northern European populations, and whether early life factors influenced susceptibility to occupational cleaning's unhealthy effects. METHODS: The RHINE III questionnaire study assessed occupational cleaning in 13,499 participants. Associations with respiratory symptoms, asthma and self-reported COPD were analysed with multiple logistic regressions, adjusting for sex, age, smoking, educational level, parent´s educational level, BMI and participating centre. Interaction of occupational cleaning with early life disadvantage (maternal smoking, severe respiratory infection <5 years, born during winter months, maternal age at birth >35 years) was investigated. MAIN RESULTS: Among 2138 ever-cleaners the risks of wheeze (OR 1.4, 95% CI 1.3-1.6), adult-onset asthma (1.5 [1.2-1.8]) and self-reported COPD (1.7 [1.3-2.2]) were increased. The risk increased with years in occupational cleaning (adult-onset asthma: ≤1 year 0.9 [0.7-1.3]; 1-4 years 1.5 [1.1-2.0]; ≥4 years 1.6 [1.2-2.1]). The association of wheeze with cleaning activity ≥4 years was significantly stronger for those with early life disadvantage than in those without (1.8 [1.5-2.3] vs. 1.3 [0.96-1.8]; pinteraction 0.035). CONCLUSIONS: Occupational cleaners had increased risk of asthma and self-reported COPD. Respiratory symptom risk was particularly increased in persons with factors suggestive of early life disadvantage. We hypothesize that early life disadvantage may increase airway vulnerability to harmful exposure from cleaning agents later in life.

Longterm follow-up in European respiratory health studies - patterns and implications.

BACKGROUND: Selection bias is a systematic error in epidemiologic studies that may seriously distort true measures of associations between exposure and disease. Observational studies are highly susceptible to selection bias, and researchers should therefore always examine to what extent selection bias may be present in their material and what characterizes the bias in their material. In the present study we examined long-term participation and consequences of loss to follow-up in the studies Respiratory Health in Northern Europe (RHINE), Italian centers of European Community Respiratory Health Survey (I-ECRHS), and the Italian Study on Asthma in Young Adults (ISAYA). METHODS: Logistic regression identified predictors for follow-up participation. Baseline prevalence of 9 respiratory symptoms (asthma attack, asthma medication, combined variable with asthma attack and/or asthma medication, wheeze, rhinitis, wheeze with dyspnea, wheeze without cold, waking with chest tightness, waking with dyspnea) and 9 exposure-outcome associations (predictors sex, age and smoking; outcomes wheeze, asthma and rhinitis) were compared between all baseline participants and long-term participants. Bias was measured as ratios of relative frequencies and ratios of odds ratios (ROR). RESULTS: Follow-up response rates after 10 years were 75% in RHINE, 64% in I-ECRHS and 53% in ISAYA. After 20 years of follow-up, response was 53% in RHINE and 49% in I-ECRHS. Female sex predicted long-term participation (in RHINE OR (95% CI) 1.30(1.22, 1.38); in I-ECRHS 1.29 (1.11, 1.50); and in ISAYA 1.42 (1.25, 1.61)), as did increasing age. Baseline prevalence of respiratory symptoms were lower among long-term participants (relative deviations compared to total baseline population 0-15% (RHINE), 0-48% (I-ECRHS), 3-20% (ISAYA)), except rhinitis which had a slightly higher prevalence. Most exposure-outcome associations did not differ between long-term participants and all baseline participants, except lower OR for rhinitis among ISAYA long-term participating smokers (relative deviation 17% (smokers) and 44% (10-20 pack years)). CONCLUSIONS: We found comparable patterns of long-term participation and loss to follow-up in RHINE, I-ECRHS and ISAYA. Baseline prevalence estimates for long-term participants were slightly lower than for the total baseline population, while exposure-outcome associations were mainly unchanged by loss to follow-up.

Increased prevalence of chronic obstructive pulmonary disease in a general population.

BACKGROUND: Prevalence of COPD is increasing worldwide, and there is need for regularly updated estimates of COPD prevalence and risk factors. METHODS: In the Norwegian Hordaland County Cohort Study (HCCS), 1664 subjects aged 35-90 yrs answered questionnaires and performed spirometry in 2003-05. We estimated COPD prevalence and analysed risk factors for COPD with logistic regression. RESULTS: In a previous study phase, prevalence of GOLD-defined COPD was 7%. Eight years later, corresponding prevalence was 14%. Seventy % of the subjects experienced respiratory symptoms. Only 1 out of 4 had a physician's diagnosis. Significant risk factors for COPD were sex, age, smoking habits and pack-years. Men had 1.7 (OR, 95% CI 1.2, 2.3) higher odds for COPD than women. Subjects above 65 yrs had 10.3 (OR, 95% CI 6.4, 16.5) times higher odds for COPD than subjects below 40 yrs. Heavy smokers had 4.2 (OR, 95% CI 2.6, 6.7) times higher odds for COPD than subjects with <10 pack-years. When compared with the previous study phase, age and smoking status had roughly the same associations with COPD prevalence. Educational level and male gender, on the other hand, had less effect on COPD prevalence in 2005 than in 1997, while pack years were more important in 2005 than in 1997. CONCLUSIONS: Prevalence of GOLD defined COPD has increased from 7% to 14% in nine years. Although the risk factors remain the same, the strength of associations vary. There is still substantial under diagnosis in COPD, and better disease awareness and diagnostic routines are needed.

Mortality by level of emphysema and airway wall thickness.

RATIONALE: There is limited knowledge of the prognostic value of quantitative computed tomography (CT) measures of emphysema and airway wall thickness (AWT) on mortality. OBJECTIVES: To examine 8-year mortality in relation to CT-measured emphysema and AWT, and assess if potential impact of these predictors remained after adjustment for lung function. METHODS: In the Norwegian GenKOLS study of 2003-2005, 947 ever-smokers (49% with COPD) aged 40-85 years performed spirometry and CT examination. Mortality data from 2003-2011 were gathered from the Norwegian Cause of Death Registry. CT emphysema % low-attenuation areas (%LAA) and standardized measure for AWT (AWT-Pi10) were main predictors. We performed Laplace regression for survival data, estimating survival time for specified population percentiles within each emphysema category. Models were adjusted for sex, FEV1, COPD status, age, body mass index, smoking, and inflation level. MEASUREMENTS AND MAIN RESULTS: During 8-year follow-up all-cause mortality rate was 15%. Although 4% of the subjects with %LAA less than 3 died, 18% with %LAA 3-10 and 44% with %LAA greater than or equal to 10 died. After adjustment, the comparable percentile subjects with medium and high emphysema had 19 months shorter survival than subjects who died in the lowest emphysema category. Subjects with %LAA greater than or equal to 10 had 33 and 37 months shorter survival than the lowest emphysema category with regard to respiratory and cardiovascular mortality, respectively. No significant associations were found between %LAA and cancer and lung cancer mortality. AWT did not predict mortality independently, but a positive interaction with emphysema was observed. CONCLUSIONS: AWT affected mortality with increasing degree of emphysema, whereas CT measure of emphysema was a strong independent mortality predictor.

The adult incidence of asthma and respiratory symptoms by passive smoking in uterus or in childhood.

The effects of pre- or postnatal passive smoking on the adult incidence of asthma have not been reported previously. Between 1985 and 1996/1997, we conducted an 11-year community cohort study on the incidence of asthma and respiratory symptoms in Western Norway. The cohort included 3,786 subjects aged 15 to 70 years, of which 2,819 were responders at both baseline and follow-up. The incidence of asthma and five respiratory symptoms by self-reported exposure to maternal smoking in utero and in childhood, as well as smoking by other household members in childhood, was examined. After adjustment for sex, age, education, hay fever, personal smoking, and occupational exposure, maternal smoking was associated with asthma, phlegm cough, chronic cough, dyspnea grade 2, attacks of dyspnea, and wheezing, with odds ratios (95% confidence intervals [CI]) of 3.0 (1.6, 5.6), 1.7 (1.1, 2.6), 1.9 (1.2, 3.0), 1.9 (1.2, 3.0), 2.0 (1.3, 3.0), and 1.4 (0.9, 2.2), respectively. The adjusted attributable fractions (95% CI) of the adult incidence of asthma were 17.3% (5.2, 27.9) caused by maternal smoking and 9.3% (95% CI, -23.2, 33.2) caused by smoking by other household members. Exposure to pre- and postnatal smoking carries a substantial risk for developing adult asthma and respiratory symptoms.