Search

Background: Spirometric restriction, defined as a reduced forced vital capacity (FVC) with a preserved FEV 1 /FVC ratio, is associated with increased respiratory and non-respiratory comorbidities and all-cause mortality in adulthood. Little is known about the early origins of this condition. We sought to identify early-life risk factors for spirometric restriction in adult life., Methods: In this longitudinal, multicohort, population-based study, we used data from the Tucson Children's Respiratory Study (TCRS), which recruited 1246 healthy infants at birth between April 1980, and October 1984, in Tucson, AZ, USA. Questionnaires were answered by the primary caregiver at enrolment, immediately after the child's birth, and multiple follow-up questionnaires were completed through childhood and adulthood. At the age of 22, 26, 32, and 36 years, lung function was measured with spirometry. At each survey, three mutually exclusive spirometric patterns were defined: (1) normal (FEV 1 /FVC ≥10th percentile and FVC ≥10th percentile); (2) restrictive (FEV 1 /FVC ≥10th percentile and FVC <10th percentile); and (3) obstructive (FEV 1 /FVC <10th percentile, independent of FVC). Data on demographic features and parental health factors were collected from questionnaires; pregnancy and perinatal data (including nutritional problems) and birth measurements were obtained from medical records; and weight, height, and body-mass index (BMI) during childhood (age 6-16 years) were measured by study nurses. The associations between early-life risk factors and spirometric patterns were assessed by multivariate multinomial logistic regression analysis, adjusted for survey year, sex, and race-ethnicity. Significant risk factors were further tested for replication in the Swedish Child (Barn), Allergy, Milieu, Stockholm, Epidemiological (BAMSE; n=1817; spirometry surveys were done at age 24 years) survey and the UK Manchester Asthma and Allergy Study (MAAS; n=411; spirometry surveys were done at age 18 years) birth cohorts, and fixed-effect meta-analyses of relative risk ratios (RRRs) from multinomial logistic regression models were done to generate a pooled estimate of the effect across the three cohorts. Measurements of body composition (MAAS; n=365) and total lung capacity (TCRS; n=173 and MAAS; n=407) were also available for a subset of participants., Findings: Of 1246 healthy infants included in TCRS, for the present study we included data for 652 participants who had at least one set of spirometry data, contributing up to 1668 observations. In the TCRS cohort, results from the multivariate models showed that maternal nutritional problems during pregnancy (RRR 2·48 [95% CI 1·30-4·76]; p=0·0062), being born small for gestational age (birthweight <10th percentile; 3·26 [1·34-7·93]; p=0·0093), and being underweight in childhood (BMI-for-age <5th percentile; 3·54 [1·35-9·26]; p=0·010) were independent predictors of spirometric restriction in adult life. Associations between being small for gestational age (p=0·0028) and underweight in childhood (p<0·0001) with adult spirometric restriction were supported by the results of meta-analysis of data from all three cohorts. In the MAAS cohort, having a low lean BMI (ie, <10th percentile) at age 11 years predicted adult (age 18 years) spirometric restriction (RRR 3·66 [1·48-9·02]; p=0·0048). These associations of spirometric restriction with small for gestational age, childhood underweight, and low lean BMI in childhood were verified in participants with spirometric restriction who had diminished total lung capacity, indicating that these factors specifically increase the risk of lung restriction., Interpretation: Poor growth and nutritional deficits in utero and throughout childhood precede and predict the development of spirometric restriction in adult life. Strategies to improve prenatal and childhood growth trajectories could help to prevent spirometric restriction and its associated morbidity and mortality burden., Funding: National Institutes of Health., Competing Interests: Declaration of interests WJM has received grant funding for this work from the National Institutes of Health; funding from the National Institutes of Health and the Cystic Fibrosis Foundation outside of the submitted work; and personal fees from the Cystic Fibrosis Foundation, the American Thoracic Society, and the American College of Chest Physicians outside of the submitted work. AC has received personal fees from Novartis, Thermo Fisher Scientific, Philips, Sanofi, Stallergenes Greer, and AstraZeneca outside of the submitted work. AS and CSM are supported by the NIHR Manchester Biomedical Research Centre. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alcohol intake has been inconsistently associated with lung function levels in cross-sectional studies. The goal of our study was to determine whether longitudinally assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed with four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories ("never", "inconsistent", or "persistent drinker"). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never-drinkers, persistent drinkers had higher FVC (coefficient: 157 mL, p < 0.001), but lower FEV 1 /FVC ratio (-2.3%, p < 0.001). Differences were due to a slower decline of FVC among persistent than among never-drinkers (p = 0.003), and these trends were present independent of smoking status. Inconsistent drinking showed similar, but weaker associations. After adjustment for potential confounders, light-to-moderate alcohol consumption was associated with a significantly decreased rate of FVC decline over adult life., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Rationale: Most patients who develop persistent airflow limitation do so either as a manifestation of chronic obstructive pulmonary disease that is largely related to smoking or as a consequence of persistent asthma. We sought to compare the natural course of lung function associated with persistent airflow limitation in subjects with and without asthma from early to late adult life., Methods: We studied 2552 participants aged 25 or more who had multiple questionnaire and lung function data from the long-term prospective population-based Tucson Epidemiological Study of Airway Obstructive Disease. Persistent airflow limitation was defined as FEV(1)/FVC ratio consistently < 70% in all completed surveys subsequent to the first survey with airflow limitation. Participants were divided into nine groups based on the combination of their physician-confirmed asthma status (never, onset < or = 25 years, or onset > 25 years) and the presence of airflow limitation during the study follow-up (never, inconsistent, or persistent)., Results: Among subjects with an asthma onset < or = 25 years, blood eosinophilia increased significantly the odds of developing persistent airflow limitation (adjusted ORs: 3.7, 1.4-9.5), whereas cigarette smoking was the strongest risk factor for persistent airflow limitation among non-asthmatics and among subjects with asthma onset after age 25 years. Among subjects with persistent airflow limitation, the natural course of lung function differed between subjects with asthma onset < or = 25 years and non-asthmatics, with the former having lower FEV(1) levels at age 25 (predicted value for a 175-cm tall male of 3400 versus 4090 ml, respectively; p<0.001) and the latter having greater FEV(1) loss between age 25 and 75 (1590 versus 2140 ml; p=0.003)., Conclusion: In subjects who have asthma onset before 25 years of age and persistent airflow limitation in adult life, the bulk of the FEV(1) deficit is already established before age 25 years.

Using an in-line, real-time, in vivo exposure system, we investigated whether acute adverse effects of diesel exhaust (DE*) exposure involve neurogenic inflammation in the lungs via sensory nerve C fibers. A total of 168 female F344 rats (175 g, 8 weeks old) were randomly assigned to pretreatment with capsaicin or saline to deplete C-fiber neurotransmitters. In a 2 x 3 factorial design, groups of animals were then exposed nose-only to a low level of DE (LDE, 35.3 microg/m3), a high level of DE (HDE, 632.9 microg/m3), or side-stream cigarette smoke (CS, 0.4 mg/m3). Two control groups were exposed whole body to filtered air in the animal room (fRA) or unfiltered air in the diesel engine room (eRA), respectively. DE was taken directly from a heavy-duty Cummins N14 research engine operated at 75% throttle (California Air Resources Board [CARB] 8, mode 6). Exposure to DE or air was 4 hours/day, 5 days/week, for 3 weeks. Exposure to CS was for 4 hours/day for 7 days. Involvement of neurogenic inflammation in the response to DE or CS was assessed via comparison of plasma extravasation, a sensitive endpoint of neurogenic inflammation, between rats with and without capsaicin pretreatment. Lung injury was assessed via analysis of proinflammatory cytokines, respiratory permeability, and histopathology. Moreover, whether DE exposure affected the molecular mechanisms of neurogenic inflammation was analyzed through quantification of substance P (SP) and its primary neurokinin-1 (NK1) receptor at the gene and protein levels and through neutral endopeptidase (NEP) activity. DE and CS exposure induced dose-dependent plasma extravasation, which may play an important role in initiating the associated lung inflammation and injury. Exposure of rats to DE affected the SP signaling pathway as indicated by overexpression of the NK1 receptor or reduction of SP in the lung tissue. DE exposure consistently inactivated tissue NEP, a key factor that switches neurogenic inflammation from its physiological and protective functions to a role that increases and perpetuates lung injury. The roles of these overlapping neurokininergic mechanisms in the initiation of DE-associated lung injury are plausible, and these changes may contribute to DE-associated respiratory disorders. Capsaicin rats followed the same trends as those of saline animals when exposed to DE or CS: capsaicin rats did not have significantly different plasma extravasation in the airways or lung parenchyma compared to their corresponding controls. Histopathology evaluation likewise demonstrated the same degree of tissue changes, such as edema and alveolar macrophage collection, in capsaicin and saline rats after the same level of DE exposure. In summary, our data suggest that neurokininergic mechanisms may have been involved in DE-induced inflammatory conditions in rat lung but that C fibers did not appear to be involved under these exposure conditions. We believe that time-course or protein knockdown/knockout animal studies are required to characterize further the role of neurokininergic mechanisms in DE-induced lung injury.

Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.

Several studies have demonstrated that smokers who are able to break the habit generally experience reductions in respiratory symptoms and improvement in pulmonary function; however, far less attention has been given to smokers who are unsuccessful in their attempts at quitting. Recent reports have suggested that these subjects (restarters) may have steeper rates of decline in pulmonary function than subjects never attempting to quit smoking. In this study, we compared rates of decline in FEV1 between restarters and subjects who remained current, ex-smokers, or never-smokers throughout the observation period. The results showed that, in both sexes, subjects who attempt to quit the habit and then restart have significantly steeper rates of decline in their FEV1 than subjects who continue smoking uninterrupted. Female restarters also have significantly steeper rates of decline in FEV1 than ex-smokers. These effects were independent of the amount smoked and respiratory diseases.

Objective: To obtain spirometry and maximal respiratory pressure (MRP) reference values for elderly persons., Design: Survey., Setting: General community., Participants: Four hundred seventy-one healthy ambulatory white women and men age 65+ years., Methods: A stringent spirometry quality assurance program exceeded American Thoracic Society recommendations. A "healthy" subgroup of 176 women and 112 men between the ages of 65- and 85 years were identified by excluding those with conditions that negatively influenced FEV1 in a multiple regression analysis. Reference equations and normal ranges for FEV1, FVC, FEF25-75%, peak flow, and maximal inspiratory and expiratory pressures (MRPs) were determined from the healthy group with good quality maneuvers., Results: Less than 10% of the subjects were unable to perform three acceptable spirometry maneuvers and ten MRP maneuvers. When the age and height corrected FEV1s from this group were compared with other spirometry reference studies, mean values from the women were nearly identical to those from Morris, while these men had substantially lower FEV1 values (by 0.3- to 0.5L) than elderly men in Crapo's study. Mean peak flow was over 20% higher when compared with previous studies, suggesting greater initial expiratory effort by our subjects. The maximal inspiratory pressure (MIP) values were about 20% higher than those reported by the Cardiovascular Health Study, perhaps because five MIP maneuvers were always performed., Conclusion: Spirometry and MRP reference values used for elderly patients should come from population studies using similar techniques and with large numbers of subjects over age 65 years.

Numerous population studies have reported that pulmonary function following the adolescent growth phase appears to be in a steady-state, where there is little or no growth occurring up to 40 yrs of age. We examined longitudinal forced expiratory volume in one second (FEV1), changes using three different statistical approaches to determine which subjects actually have significant trends during this period. Participants, who were employees at a metal processing plant, underwent quarterly spirometry for up to 10 yrs. Test results up to 33 yrs of age were included in the analysis. Each subject's FEV1 data was first analysed using simple linear regression (SLR) to test for a statistically significant linear slope. Next, each subject's data were fitted using bootstrap sampling (BSS) of their original data, to yield reduced estimates of the slope variances and increase the power of detecting a significant trend. And thirdly, we fitted a regression breakpoint (BKPT) model to the data to find those subjects who may have piecewise linear growth or decline in function. All analyses were stratified, based on smoking status. Subjects included 111 nonsmokers and 110 smokers. Among the nonsmokers, 34 subjects had significant slopes using SLR, an additional three using BSS, and only two with BKPT. Among the smokers, 36 had a significant trend using SLR, 7 were added using BSS, and no additional subjects with BKPT. We conclude that in young adult males lung function is not in a steady-state and that as many as 40% have a significant slope, either positive or negative.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study recently developed longitudinal techniques are used to examine the relationship between respiratory symptoms, smoking and pulmonary function measures in elderly subjects. The subjects were participants in the Tucson Epidemiological Study of Airways Obstructive Disease, aged > or = 55 yrs at the first survey 1972-1973, who had received pulmonary function testing and completed questionnaires in at least one of the six selected surveys. There were 633 males and 891 females, with up to 14 yrs follow-up included in the analysis. Based on their questionnaire responses, subjects were classified according to their respiratory symptoms and smoking habits at each survey. The pulmonary function testing included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and their ratio (FEV1/FVC). The pulmonary function data were analysed gender specific, with and without stratifying on vital status. The results indicate that respiratory symptoms are generally associated with lower levels of lung function, and that the impairment associated with chronic cough was observed predominantly in male subjects. The negative association of smoking was apparent in most measures, but was largest and most progressive in the FEV1/FVC ratios. Ex-smokers, in all cases, had better lung function values than current smokers, but their mean curves were always significantly below the values of nonsmokers.

In this study we examined the longitudinal effects of smoke exposure on lung function in a cohort of New Zealand children observed from 9 to 15 yr of age. Possible exposures included in utero exposure from mothers smoking during pregnancy, passive smoke from parents, and active smoking by the children. Lung function measures of forced expiratory volume in one second (FEV1) and vital capacity (VC) were measured biennially and ratios (FEV1/VC) were computed. The data were analyzed using longitudinal methodology, and all subjects with at least one pulmonary function test and responses to the questions concerning smoke exposures were included (n = 634). Subjects reporting wheeze or asthma were examined as a separate subgroup. In the whole cohort, no significant detrimental effects were detected for absolute FEV1 or VC in either sex, related to active or passive smoke exposures. Parental smoking was, however, associated with persistent but mild and nonprogressive impairment of the FEV1/VC ratio in males, an effect that was present at the time lung function measurements were first made. This effect was not seen in females. In children with reported wheeze or asthma, parental smoking had progressive, more serious, and clinically significant effects on the FEV1/VC ratio among adolescents of both sexes, causing a mean reduction in FEV1/VC ratios by age 15 of 3.9% in males and 2.3% in females, in contrast to the observed increase in FEV1/VC ratios with age seen in nonexposed wheezing children. We conclude that passive smoking is a major contributing factor to the development and persistence of airflow limitation in wheezing children.

Numerous studies have examined the natural time course of human lung function growth and decline throughout life. In most of these studies the investigators used statistical models that required a priori assumptions concerning the underlying form or structure of the lung function data, thus introducing possible biases. In this study we used recently developed nonparametric regression (spline) techniques to describe the evolution of lung function measures with age. This procedure yields an optimally fitted smooth curve through the data and estimates of the process velocity and does not require assumptions concerning the underlying shape of the data curves. The lung function growth-velocity curves are used to estimate the age of growth cessation. This technique was applied to the FVC, FEV1, and the FEV1/FVC ratios of 1,295 females and 1,230 males who were tested in at least one of the first nine surveys of the Tucson epidemiologic study of airway obstructive diseases. Data were analyzed stratified according to gender, smoking status, and respiratory symptoms or diseases. The results indicate large differences between the fitted FEV1 and FEV1/FVC smoothed curves of the various subgroups compared with asymptomatic nonsmokers. These differences were most pronounced in the adult symptomatic smokers, who had higher rates of lung function loss that also began at earlier ages, for both sexes. No significant differences were observed between asymptomatic and symptomatic nonsmokers, most likely because of the reduced number of symptomatic nonsmokers, particularly among the males.

The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette. There were 690 subjects who reported smoking regularly in at least one survey, over age 15. After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields. In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked). The effects were more pronounced for past than for current doses. However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

A sample population of healthy nonsmoking male (n = 416) and female (n = 608) subjects derived from all non-Hispanic white subjects 5 to 60 yr of age enrolled in the Tucson Epidemiological Study of Airway Obstructive Disease was studied to evaluate the temporal relationships between various pulmonary function measures and somatic growth. Pulmonary function measures derived from the maximal expiratory flow volume (MEFV) curve included FVC, FEV1, maximal expiratory flow after 50% of vital capacity had been expired (Vmax50), and maximal midexpiratory flow (FEF25-75). The lung function and somatic growth longitudinal data were characterized by a nonparametric polynomial smoothing spline model. This procedure yields an optimal fitted curve through the data, an estimate of the growth velocity curve, and 95% confidence bands. Temporal relationships between the fitted growth curves were determined examining the ages at which the growth velocity peaks (GVP) occur. In addition, the age of growth cessation was estimated using lower limits of the 95% confidence bands of each growth velocity curve. The results indicate that the point estimates of the somatic GVPs precede all peak lung function measurements derived from the MEFV curve in both males and females. The only statistically significant difference between when the GVPs for somatic growth and functional lung growth occurred was for FEV1 and FEF25-75 in males, though similar trends were apparent in all other variables, suggesting that the timing of maximal body growth velocity precedes that of maximal lung functional growth and that the early growth spurt in females includes the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

A mathematical procedure is described for examining growth velocity rates of lung function (FEV1) in relationship to somatic growth and maturation. This procedure uses a polynomial smoothing spline model to yield a fitted curve through the data and to estimate the process first derivatives (i.e. growth velocity curves). We demonstrate this technique using data from children and adolescents enrolled in the Tucson Epidemiological Study of Airway Obstructive Diseases. The study group consisted of 772 healthy normal subjects, aged 3 to 25 y. The results for the normal subjects (male and female) indicate that the growth velocity peak (GVP) of somatic growth leads the GVP of functional growth (FEV1) by approximately 7 and 11 mo for females and male subjects, respectively, and that the GVP of maturation lags behind that of functional growth (FEV1) by approximately 1 y (male and female subjects). In addition, the normal subjects' growth velocity curves for FVC and FEV1/FVC were examined. The FEV1/FVC ratio was consistently high, and its growth velocity was not significantly different than 0 over the age range studied. This suggests that in normal children, the GVP seen in FEV1 is primarily due to a GVP in vital capacity or lung vol, rather than to a direct effect on expiratory flow rates alone. From this study we concluded that the polynomial smoothing spline procedure can adequately model the inherently noisy pulmonary function data and additionally yield an accurate estimate of the process first derivative.