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In the non-selected birth cohort Tucson Children's Respiratory Study, early sensitisation to Alternaria was associated with increased airway hyper-responsiveness (AHR) into adult life among non-asthmatics. The increase in AHR was of a similar magnitude to that seen for Alternaria sensitised asthmatics and was primarily evident among those who were overweight or obese. In contrast, there was no significant association between early sensitisation to aeroallergens other than Alternaria and AHR among non-asthmatics. Why this group of Alternaria sensitised individuals without asthma demonstrated increased AHR of a magnitude similar to asthmatics is unknown and requires further investigation. [ABSTRACT FROM AUTHOR]

Rationale: Low maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline.Objectives: We aimed to determine if there were individuals with a distinct, persistently low lung function trajectory in the CRS (Tucson Children's Respiratory Study).Methods: The CRS, an ongoing birth cohort study, enrolled 1,246 participants between 1980 and 1984. Latent class linear mixed effects modeling of the ratio of FEV1 to FVC was used to identify distinct lung function trajectories among participants with two or more spirometry measurements between ages 11 and 32 years.Measurements and Main Results: Among 599 participants with 2,142 observations, a model with two distinct trajectories (a low trajectory [n = 56; 9.3%] and a normal trajectory) fit the data significantly better than a model with only one trajectory (P = 0.0007). As compared with those with a normal trajectory, participants with a persistently low trajectory were more likely to have a history of maternal asthma (20.0% vs. 9.9%; P = 0.02); early life lower respiratory illness caused by respiratory syncytial virus (41.2% vs. 21.4%; P = 0.001); and physician-diagnosed active asthma at age 32 years (43.9% vs. 16.2%; P < 0.001). Individuals with a persistently low trajectory also demonstrated lower lung function as measured by average maximal expiratory flow at functional residual capacity during infancy and at age 6 years.Conclusions: A distinct group of individuals in a nonselected population demonstrates a persistently low lung function trajectory that may be partly established at birth and predisposes them to chronic obstructive pulmonary disease later in life. [ABSTRACT FROM AUTHOR]

Rationale: Lung function and growth are adversely associated with nitrogen dioxide (NO 2 ) exposure. Lower levels of circulating club cell secretory protein (CC16) in childhood are also associated with subsequent decreased lung function. NO 2 exposure may induce epithelial damage in lungs and alter club cell proliferation and morphology. Objectives: To determine if increased ambient NO 2 levels at participants' home addresses in early life were associated with decreased levels of CC16 from age 6 to 32 years. Methods: Participants were enrolled at birth in the Tucson Children's Respiratory Study and had circulating CC16 measured at least once between age 6 and 32. Linear mixed models were used to determine the association between estimated ambient NO 2 exposure at participants' home address at birth or age 6 with CC16 levels from age 6 to 32. Measurements and Main Results: NO 2 exposures at birth or age 6 were available for 777 children with one or more CC16 measurement. We found a negative association between NO 2 exposure and CC16 levels, with a 4.7% (95% confidence interval, -8.6 to -0.7) decrease in CC16 levels from age 6 to 32 per interquartile range increase in NO 2 exposure (6.0 ppb) at the participants' birth address. We observed modification by race (p interaction = 0.04), with stronger associations among participants with at least one black parent (-29.6% [95% confidence interval, -42.9% to -13.2%] per interquartile range). NO 2 at participant's age 6 address was not significantly associated with CC16 levels (-1.9%; 95% confidence interval, -6.3 to 2.6). Conclusions: Higher exposure to NO 2 at birth is associated with persistently low levels of CC16 from 6 to 32 years.

In the non-selected birth cohort Tucson Children's Respiratory Study, early sensitisation to Alternaria was associated with increased airway hyper-responsiveness (AHR) into adult life among non-asthmatics. The increase in AHR was of a similar magnitude to that seen for Alternaria sensitised asthmatics and was primarily evident among those who were overweight or obese. In contrast, there was no significant association between early sensitisation to aeroallergens other than Alternaria and AHR among non-asthmatics. Why this group of Alternaria sensitised individuals without asthma demonstrated increased AHR of a magnitude similar to asthmatics is unknown and requires further investigation., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established., Methods: As part of the prospective Tucson Children's Respiratory Study, LRIs during the first 3 years of life were ascertained by pediatricians. Spirometry was performed at ages 11, 16, 22, and 26 years. The occurrence of asthma/wheeze during the previous year was ascertained at ages 11, 13, 16, 18, 22, 24, 26, and 29 years. Longitudinal random effects models and generalized estimating equations were used to assess the relation of LRIs to lung function and asthma., Results: Compared with participants without early-life LRIs, those with pneumonia had the most severe subsequent lung function impairment, with mean ± SE deficits of -3.9% ± 0.9% (P < .001) and -2.5% ± 0.8% (P = .001) for pre- and post-bronchodilator FEV1:FVC ratio from age 11 to 26 years, respectively. Pneumonia was associated with increased risk for asthma (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.11-3.44) and wheeze (OR: 1.94; 95% CI: 1.28-2.95) over the same age range. Early non-pneumonia LRIs were associated with mildly impaired pre-bronchodilator FEV1 (-62.8 ± 27.9 mL, P = .024) and FEV1:FVC ratio (-1.1 ± 0.5%, P = .018), and wheeze (OR: 1.37; 95% CI: 1.09-1.72)., Conclusions: Early pneumonia is associated with asthma and impaired airway function, which is partially reversible with bronchodilators and persists into adulthood. Early pneumonia may be a major risk factor for adult chronic obstructive pulmonary disease., (Copyright © 2015 by the American Academy of Pediatrics.)

Background: Insomnia has been associated with mortality risk, but whether this association is different in subjects with persistent vs intermittent insomnia is unclear. Additionally, the role of systemic inflammation in such an association is unknown., Methods: We used data from a community-based cohort to determine whether persistent or intermittent insomnia, defined based on persistence of symptoms over a 6-year period, was associated with death during the following 20 years of follow-up. We also determined whether changes in serum C-reactive protein (CRP) levels measured over 2 decades between study initiation and insomnia determination were different for the persistent, intermittent, and never insomnia groups. The results were adjusted for confounders such as age, sex, body mass index, smoking, physical activity, alcohol, and sedatives., Results: Of the 1409 adult participants, 249 (18%) had intermittent and 128 (9%) had persistent insomnia. During a 20-year follow-up period, 318 participants died (118 due to cardiopulmonary disease). In adjusted Cox proportional-hazards models, participants with persistent insomnia (adjusted hazards ratio [HR] 1.58; 95% confidence interval [CI], 1.02-2.45) but not intermittent insomnia (HR 1.22; 95% CI, 0.86-1.74) were more likely to die than participants without insomnia. Serum CRP levels were higher and increased at a steeper rate in subjects with persistent insomnia as compared with intermittent (P = .04) or never (P = .004) insomnia. Although CRP levels were themselves associated with increased mortality (adjusted HR 1.36; 95% CI, 1.01-1.82; P = .04), adjustment for CRP levels did not notably change the association between persistent insomnia and mortality., Conclusions: In a population-based cohort, persistent, and not intermittent, insomnia was associated with increased risk for all-cause and cardiopulmonary mortality and was associated with a steeper increase in inflammation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Asthma and chronic obstructive pulmonary disease co-exist in a significant proportion of patients. Whether asthma increases mortality risk among subjects with airflow limitation remains controversial. We used data from 2121 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease cohort. At enrolment (1972-1973), participants completed questionnaires and lung function tests. Participants were categorised into four groups based on the combination of airflow limitation (AL; forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%) and physician-confirmed asthma at baseline. Vital status as of January 2011 was assessed through the National Death Index. Cox proportional hazards models were used to test differences in mortality risk across the four airflow limitation/asthma groups. In multivariate Cox models, the AL+/asthma+ group had a 114% increased mortality risk during follow-up compared with the AL-/asthma- group (adjusted HR 2.14; 95% CI 1.64-2.79). The corresponding hazard ratios were 1.09 (95% CI 0.89-1.34) and 1.34 (95% CI 1.14-1.57) for the AL-/asthma+ and AL+/asthma- groups, respectively. Among subjects with airflow limitation, asthma was associated with increased mortality risk (HR 1.58, 95% CI 1.17-2.12). However, this increased risk was substantially reduced and no longer significant after further adjustment for baseline FEV1 levels. Similar results were obtained when airflow limitation was defined as FEV1/FVC less than the lower limit of normal. In a population-based cohort, subjects with concomitant airflow limitation and asthma had an increased risk of dying, which was mainly related to their baseline lung function deficits., (Copyright ©ERS 2015.)

Rationale: Risk of subsequent asthma-like symptoms after early-life lower respiratory illness (LRI) caused by respiratory syncytial virus (RSV) is increased during the first decade of childhood and diminished thereafter by adolescence., Objectives: To determine the relation of early-life RSV-LRI on adult asthma-like symptoms and its interactive role with adult smoking., Methods: A total of 1,246 nonselected infants were enrolled at birth and prospectively followed. Virologically confirmed RSV-LRIs were assessed during the first 3 years of life. At age 22, 24, 26, and 29 years, current asthma and smoking behavior were evaluated by questionnaire. Peak flow variability was assessed at age 26 and expressed as amplitude % mean. A longitudinal analysis was used to investigate the relation of RSV-LRI and active smoking to adult outcomes., Measurements and Main Results: Neither RSV-LRI nor active smoking were directly associated with increased current adult asthma or peak flow variability. However, there was a significant interaction between RSV-LRI and active smoking in relation to current asthma (P for interaction = 0.004) and peak flow variability (P for interaction = 0.04). Among subjects with early RSV-LRI, those who actively smoked were 1.7 times more likely to have current asthma (95% confidence interval, 1.2-2.3; P = 0.003) and had greater amplitude % mean (10.0% vs. 6.4%; P = 0.02) than nonsmokers. Among subjects without early RSV-LRI, there was no difference in asthma risk or peak flow variability between active smokers and nonsmokers., Conclusions: Smoking is associated with increased risk of having asthma in young adults who had RSV-LRI in early life but not among subjects without these illnesses.

Background: Cross-sectional reports have suggested that, among active smokers, previous exposure to parental smoking may increase susceptibility to development of chronic obstructive pulmonary disease. We assessed prospectively whether parental smoking enhances the effects of active smoking on early deficits of lung function in young adults., Methods: We used data from the prospective birth cohort, the Tucson Children's Respiratory Study. Maternal and paternal smoking was assessed via questionnaires completed by the parents at the time of the participant's birth. Active smoking by participants was assessed via personal questionnaires completed at ages 16 (YR16), 22 and 26 years. Four groups were generated based on the combination of parental and active smoking. Lung function parameters, including forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio, were assessed by spirometry before and after inhalation of 180 μg of albuterol at YR11, YR16, YR22 and YR26., Results: Complete data were available for 519 participants. Pre-bronchodilator FEV1/FVC values did not differ at YR11, YR16 or YR22 by parental or active smoking. However, at YR26 participants with exposure to parental and active smoking had pre-bronchodilator FEV1/FVC levels that were, on average, 2.8% (0.9% to 4.8%; p=0.003) lower than participants who were not exposed to parental or active smoking. In contrast, subjects who were only exposed to active smoking or only exposed to parental smoking did not differ from those who were not exposed to either. Between YR11 and YR26, participants with exposure to parental and active smoking had the steepest decline in sex, age and height adjusted residuals of FEV1/FVC, FEV1, forced expiratory flow between 25% and 75% of the FVC (FEF25-75) and FEF25-75/FVC (all p values between 0.03 and <0.001)., Conclusions: Parental and active smoking act synergistically to affect early lung function deficits in young adulthood.

Background: Recent studies have suggested that a restrictive pattern assessed with a single spirometric test is associated with increased morbidity and mortality. This study was undertaken to determine demographic, clinical and mortality profiles of subjects with either a recurrent or an inconsistent restrictive spirometric pattern assessed prospectively., Methods: Data from 2048 adult participants in the population-based TESAOD study were analysed. Normal (forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) ratio >or=70% and FVC >or=80% predicted), restrictive (FEV(1)/FVC >or=70% and FVC <80% predicted) and obstructive (FEV(1)/FVC <70%) patterns were assessed at the enrollment survey in 1972 and in 11 subsequent follow-up surveys up to 1996. Demographic and clinical characteristics were measured at enrollment and vital status and cause of death were assessed at January 2005., Results: Overall, 12% of participants had a restrictive spirometric pattern at enrollment. They were less likely to be male, to smoke and to have asthma, and had lower IgE levels than subjects in the obstructive group. Among subjects with a restrictive pattern at enrollment, 38% developed an obstructive pattern during follow-up. The remaining 62% had either a recurrent (restrictive pattern >or=50% of follow-up surveys) or inconsistent (restrictive pattern <50% of follow-up surveys) longitudinal restrictive pattern. The recurrent and inconsistent restrictive groups had increased mortality risk for all-cause (adjusted HR 1.7 (95% CI 1.3 to 2.3) and 1.9 (95% CI 1.4 to 2.6), respectively), heart disease (2.0 (95% CI 1.3 to 3.1) and 2.7 (95% CI 1.7 to 4.3)), stroke (2.4 (95% CI 0.9 to 6.3) and 3.5 (95% CI 1.2 to 9.8)) and diabetes (8.0 (95% CI 2.9 to 21.8) and 6.0 (95% CI 1.9 to 19.2))., Conclusions: The restrictive spirometric pattern identifies a pulmonary condition that is distinguishable from obstructive lung disease and is associated with an increased risk of life-threatening comorbidities.

Objective: To investigate associations between sleep disturbances and chemical odor intolerance (COI), which is the subjective report of feeling ill from common odors, such as carpet glue or pesticides., Methods: This cross-sectional study consisted of government employees and their family members (n=140; 61% women, mean age=46.3 years) derived from a stratified cluster population living in Pima County, Tucson, AZ. Subjects completed a standard survey that included sleep symptoms, a validated measure of COI, and two questions regarding anxiety and depression. Odds ratios (OR) with 95% confidence intervals (CI) were computed to test the association between COI and sleep symptoms. Stratification according to the Mantel-Haenszel method and logistic regression models were used to test for confounding and/or effect modification., Results: After adjusting for age and gender, subjects with COI were significantly more likely to report difficulty staying asleep (OR=3.06; CI=1.17-8.03), insufficient sleep (OR=3.93; CI=1.43-10.79), and nightmares (OR=3.17; CI=1.14-8.81) compared to persons without COI. Associations between COI, sleep maintenance problems and insufficient sleep were still significant after adjusting for gender and depression; however, the association between COI and nightmares became borderline., Conclusions: Compared to the non-COI, persons with COI are more likely to report sleep maintenance insomnia and insufficient sleep independent of self-reported depression. Nightmares appear to be related more to depression than to COI.

Background: Although it is defined as cough and sputum production for at least 3 months per year for at least 2 consecutive years, difficulties exist in the use of the term chronic bronchitis for clinical diagnosis. In particular, the relationship between diagnosis and symptoms has been difficult to ascertain., Study Objectives: To determine, in a large epidemiologic study, the degree to which a new self-reported diagnosis of chronic bronchitis (NCBR) satisfies the symptom criteria for that diagnosis, and to determine the relationship between self-reported physician-confirmed diagnoses and symptom criteria., Methods: We analyzed data obtained from the Tucson Epidemiologic Study of Obstructive Lung Diseases. Using responses to standardized respiratory questionnaires administered to 4,034 subjects, those with NCBRs were selected and assessed as to whether they met symptom criteria for that diagnosis. Descriptive statistics pertaining to gender, age, and smoking status were obtained. Furthermore, we determined how often symptom criteria were met among a subset of subjects with physician-confirmed self-reported diagnoses., Results: Of 481 subjects with NCBRs, only 56 subjects (11.6%) met the required symptom criteria. Men compared with women and current smokers compared with ex-smokers or neversmokers were more likely to meet symptom criteria. Four hundred fifteen of 481 subjects with NCBRs had physician-confirmed self-reported diagnoses. Of these, only 52 subjects (12.5%) met symptom criteria. Within the subgroup of subjects who met symptom criteria, higher percentages were observed in the older age groups, but this was not statistically significant., Conclusion: Only a minority of subjects with NCBRs satisfy the symptom criteria of cough and sputum production for at least 3 months per year for at least 2 consecutive years. This relationship holds true even among those with physician-confirmed self-reported diagnoses.