Cecilie Svanes

Early life origins of chronic obstructive pulmonary disease

Background: Early life development may influence subsequent respiratory morbidity. The impact of factors determined in childhood on adult lung function, decline in lung function and chronic obstructive pulmonary disease (COPD) was investigated. Methods: European Community Respiratory Health Survey participants aged 20–45 years randomly selected from general populations in 29 centres underwent spirometry in 1991–3 (n = 13 359) and 9 years later (n = 7738). Associations of early life factors with adult forced expiratory volume in 1 s (FEV1), FEV1 decline and COPD (FEV1/FVC ratio <70% and FEV1 <80% predicted) were analysed with generalised estimating equation models and random effects linear models. Results: Maternal asthma, paternal asthma, childhood asthma, maternal smoking and childhood respiratory infections were significantly associated with lower FEV1 and defined as “childhood disadvantage factors”; 40% had one or more childhood disadvantage factors which were associated with lower FEV1 (men: adjusted difference 95 ml (95% CI 67 to 124); women: adjusted difference 60 ml (95% CI 40 to 80)). FEV1 decreased with increasing number of childhood disadvantage factors (⩾3 factors, men: 274 ml (95% CI 154 to 395), women: 208 ml (95% CI 124 to 292)). Childhood disadvantage was associated with a larger FEV1 decline (1 factor: 2.0 ml (95% CI 0.4 to 3.6) per year; 2 factors: 3.8 ml (95% CI 1.0 to 6.6); ⩾3 factors: 2.2 ml (95% CI −4.8 to 9.2)). COPD increased with increasing childhood disadvantage (1 factor, men: OR 1.7 (95% CI 1.1 to 2.6), women: OR 1.6 (95% CI 1.01 to 2.6); ⩾3 factors, men: OR 6.3 (95% CI 2.4 to 17), women: OR 7.2 (95% CI 2.8 to 19)). These findings were consistent between centres and when subjects with asthma were excluded. Conclusions: People with early life disadvantage have permanently lower lung function, no catch-up with age but a slightly larger decline in lung function and a substantially increased COPD risk. The impact of childhood disadvantage was as large as that of heavy smoking. Increased focus on the early life environment may contribute to the prevention of COPD.

Childhood environment and adult atopy: results from the European Community Respiratory Health Survey.

BACKGROUND Previous literature has indicated that environmental exposures in childhood influence development of atopic sensitization. OBJECTIVE We sought to study the association between childhood environment and adult atopy. METHODS Thirteen thousand nine hundred thirty-two subjects aged 20 to 44 years from 36 areas in Europe, New Zealand, the United States, and Australia took part in the European Community Respiratory Health Survey, answering interviewer-led questionnaires and providing blood tests for measurement of specific IgE to grass, house dust mite, cat, and Cladosporium allergens. RESULTS Atopy was negatively associated with family size (OR = 0. 93; 95% CI = 0.90-0.96 per 1 sib), partly attributable to an independent protective effect of a greater number of brothers (OR = 0.92; 95% CI = 0.89-0.95 per 1 brother). Accounting for total number of siblings, no further influence was detected for number of older or younger siblings. Bedroom sharing was associated with a lower prevalence of atopy, particularly to cat allergen. A protective effect of family size and bedroom sharing could only be detected in subjects reporting no parental allergy (family size, test for interaction P =.012). The presence of a dog in the home in childhood was negatively associated with adult atopy (OR = 0.85, 95% CI = 0. 78-0.92), an effect that remained after adjustment for parental allergy, sibling allergy, and adult pet ownership. CONCLUSION Subjects from large families with brothers, shared bedrooms, and dogs in childhood were less often atopic as adults. Our findings are consistent with the hypothesis that infectious agents could inhibit development of atopy during childhood. However, in subjects with a strong genetic predisposition, environmental factors in childhood are possibly of less importance.

An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages

Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects “at risk” of developing the disease. Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20–44 years) were analysed. Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II–III. Moderate to heavy smoking (⩾15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p<0.001), with no difference between stage 0 and COPD. Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5–10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.

Parental smoking in childhood and adult obstructive lung disease: results from the European Community Respiratory Health Survey

Background: Early exposure to parental smoking appears to influence the development of the airways and predispose to respiratory symptoms. A study was undertaken to determine whether the consequences of parental smoking could be traced in adulthood. Methods: Information from interviewer-led questionnaires was available for 18 922 subjects aged 20–44 years from random population samples in 37 areas participating in the European Community Respiratory Health Survey. Lung function data were available for 15 901 subjects. Results: In men, father’s smoking in childhood was associated with more respiratory symptoms (ORwheeze 1.13 (95% CI 1.00 to 1.28); never smokers: ORwheeze 1.21 (95% CI 0.96 to 1.50)) and there was a dose-dependent association between number of parents smoking and wheeze (one: OR 1.08 (95% CI 0.94 to 1.24); both: OR 1.24 (95% CI 1.05 to 1.47); ptrend  =  0.010). A reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) was related to father’s smoking (−0.3% (95% CI −0.6 to 0)) and number of parents smoking (ptrend <0.001) among men. In women, mother’s smoking was associated with more respiratory symptoms and poorer lung function (ORwheeze 1.15 (95% CI 1.01 to 1.31), never smokers: ORwheeze 1.21 (95% CI 0.98–1.51); FEV1 −24 ml (95% CI −45 to −3); FEV1/FVC ratio −0.6% (95% CI −0.9 to −0.3)). These effects were possibly accounted for by maternal smoking in pregnancy (ORwheeze 1.39 (95% CI 1.17 to 1.65); FEV1 −23 ml (95% CI −52 to 7); FEV1/FVC ratio −0.9% (95% CI −1.3 to −0.4)) as there was no association with paternal smoking among women (interaction by sex, p<0.05). These results were homogeneous across centres. Conclusion: Both intrauterine and environmental exposure to parental tobacco smoking was related to more respiratory symptoms and poorer lung function in adulthood in this multicultural study. The age window of particular vulnerability appeared to differ by sex, postnatal exposure being important only in men and a role for prenatal exposure being more evident in women.

Trends in Perforated Peptic Ulcer: Incidence, Etiology, Treatment, and Prognosis

After increasing steeply at the beginning of the twentieth century, ulcer perforation incidence during the last decades has declined in the young and in men, and it has risen among the elderly and in women. These changes can be attributed to a cohort phenomenon: Ulcer perforation risk is particularly common in the cohorts born after the turn of the twentieth century and is less common in previous and succeeding birth cohorts. A decline in total incidence is expected with the death of the high risk cohorts. Most ulcer perforations among subjects < 75 years of age can be attributed to smoking. Subjects with a history of ulcer perforation therefore have poorer long-term survival than the general population, most pronounced for younger generations. About one of four ulcer perforations can be attributed to the use of nonsteroidal antiinflammatory drugs, a risk factor of particular importance in the elderly. Ulcer perforation was frequently treated by gastric resection in former days, whereas suture, being the first method introduced in 1887, is the method of choice today. The introduction of antibiotics improved the prognosis of ulcer perforation surgery greatly. Postoperative lethality decreased until 1950 but has remained stable since then. Lethality is higher in the elderly and is higher after gastric than after duodenal perforation. The delay before surgical treatment is a strong determinant for lethality, complication rates, and hospital costs. Treatment delay seems to have increased during the last few decades and is higher among women and the elderly. The prognosis of ulcer perforation is poorer in women owing to longer treatment delay.

Smoking cessation, lung function, and weight gain : a follow-up study

BACKGROUND Only one population-based study in one country has reported effects of smoking cessation and weight change on lung function, and none has reported the net effect. We estimated the net benefit of smoking cessation, and the independent effects of smoking and weight change on change in ventilatory lung function in the international European Community Respiratory Health Survey. METHODS 6654 participants in 27 centres had lung function measured in 1991-93, when aged 20-44 years, and in 1998-2002. Smoking information was obtained from detailed questionnaires. Changes in lung function were analysed by change in smoking and weight, adjusted for age and height, in men and women separately and together with interaction terms. FINDINGS Compared with those who had never smoked, decline in FEV1 was lower in male sustained quitters (mean difference 5.4 mL per year, 95% CI 1.7 to 9.1) and those who quit between surveys (2.5 mL, -1.9 to 7.0), and greater in smokers (-4.8 mL, -7.9 to -1.6). In women, estimates were 1.3 mL per year (-1.5 to 4.1), 2.8 mL (-0.8 to 6.3) and -5.1 mL (-7.5 to -2.8), respectively. These sex differences were not significant. FEV1 changed by -11.5 mL (-13.3 to -9.6) per kg weight gained in men, and by -3.7 mL per kg (-5.0 to -2.5) in women, which diminished the benefit of quitting by 38% in men, and by 17% in women. INTERPRETATION Smoking cessation is beneficial for lung function, but maximum benefit needs control of weight gain, especially in men.

Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey

Background: Information on the epidemiology of asthma in relation to age is limited and hampered by reporting error. To determine the change in the prevalence of asthma with age in young adults we analysed longitudinal data from the European Community Respiratory Health Survey. Methods: A self-administered questionnaire was completed by 11 168 randomly selected subjects in 14 countries in 1991–3 when they were aged 20–44 years and 5–11 years later from 1998 to 2003. Generalised estimating equations were used to estimate net change in wheeze, nocturnal tightness in chest, shortness of breath, coughing, asthma attacks in the last 12 months, current medication, “diagnosed” asthma, and nasal allergies. Results: Expressed as change in status per 10 years of follow up, subjects reporting asthma attacks in the previous 12 months increased by 0.8% of the population (95% CI 0.2 to 1.4) and asthma medication by 2.1% (95% CI 1.6 to 2.6), while no statistically significant net change was found in reported symptoms. Reported nasal allergies increased, especially in the youngest age group. Conclusions: As this cohort of young adults has aged, there has been an increase in the proportion treated for asthma but not in the proportion of those reporting symptoms suggestive of asthma. Either increased use of effective treatments has led to decreased morbidity among asthmatic subjects or those with mild disease have become more likely to label themselves as asthmatic.

Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults.

RATIONALE Few studies have investigated the factors associated with the early inception of chronic obstructive pulmonary disease (COPD). OBJECTIVES We investigated COPD risk factors in an international cohort of young adults using different spirometric definitions of the disease. METHODS We studied 4,636 subjects without asthma who had prebronchodilator FEV(1)/FVC measured in the European Community Respiratory Health Survey both in 1991 to 1993 (when they were 20-44 yr old) and in 1999 to 2002. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease fixed cut-off criterion (FEV(1)/FVC < 0.70), and two criteria based on the Quanjer and LuftiBus reference equations (FEV(1)/FVC less than lower limit of normal). COPD determinants were studied using two-level Poisson regression models. MEASUREMENTS AND MAIN RESULTS COPD incidence ranged from 1.85 (lower limit of normal [Quanjer]) to 2.88 (Global Initiative for Chronic Obstructive Lung Disease) cases/1,000/yr. Although about half of the cases had smoked less than 20 pack-years, smoking was the main risk factor for COPD, and it accounted for 29 to 39% of the new cases during the follow-up. Airway hyperresponsiveness was the second strongest risk factor (15-17% of new cases). Other determinants were respiratory infections in childhood and a family history of asthma, whereas the role of sex, age, and of being underweight largely depended on the definition of COPD used. CONCLUSIONS COPD may start early in life. Smoking prevention should be given the highest priority to reduce COPD occurrence. Airway hyperresponsiveness, a family history of asthma, and respiratory infections in childhood are other important determinants of COPD. We suggest the need for a definition of COPD that is not exclusively based on spirometry.

Underestimation of airflow obstruction among young adults using FEV1/FVC <70% as a fixed cut-off: a longitudinal evaluation of clinical and functional outcomes

Background: Early detection of airflow obstruction is particularly important among young adults because they are more likely to benefit from intervention. Using the forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) (FEV1/FVC) <70% fixed ratio, airflow obstruction may be underdiagnosed. The lower limit of normal (LLN), which is statistically defined by the lower fifth percentile of a reference population, is physiologically appropriate but it still needs a clinical validation. Methods: To evaluate the characteristics and longitudinal outcomes of subjects misidentified as normal by the fixed ratio with respect to the LLN, 6249 participants (aged 20–44 years) in the European Community Respiratory Health Survey were examined and divided into three groups (absence of airflow obstruction by the LLN and the fixed ratio; presence of airflow obstruction only by the LLN; presence of airflow obstruction by the two criteria) for 1991–1993. LLN equations were obtained from normal non-smoking participants. A set of clinical and functional outcomes was evaluated in 1999–2002. Results: The misidentified subjects were 318 (5.1%); only 45.6% of the subjects with airflow obstruction by the LLN were also identified by the fixed cut-off. At baseline, FEV1 (107%, 97%, 85%) progressively decreased and bronchial hyperresponsiveness (slope 7.84, 6.32, 5.57) progressively increased across the three groups. During follow-up, misidentified subjects had a significantly higher risk of developing chronic obstructive pulmonary disease and a significantly higher use of health resources (medicines, emergency department visits/hospital admissions) because of breathing problems than subjects without airflow obstruction (p<0.001). Conclusions: Our findings show the importance of using statistically derived spirometric criteria to identify airflow obstruction.