Longitudinal Changes In FEV1 Research Articles

Association between bronchiectasis exacerbations and longitudinal changes in FEV1 in patients from the US bronchiectasis and NTM research registry

BackgroundThis study aimed to evaluate the association between the number of non-cystic fibrosis bronchiectasis (bronchiectasis) exacerbations during baseline and follow-up (objective 1) and to identify longitudinal changes in FEV1 associated with exacerbation frequency (objective 2). MethodsThis was a retrospective cohort study of adult patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry September 2008 to March 2020. Objective 1 outcome was association between exacerbations during baseline (24 months) and 0-to-24 month and 24-to-48 month follow-up windows. Objective 2 outcomes were change in FEV1 and FEV1 % predicted over 24 months stratified by baseline exacerbation frequency. ResultsObjective 1 cohort (N = 520) baseline frequency of any exacerbations was 59.2%. Overall, 71.4% and 75.0% of patients with ≥1 baseline exacerbations had ≥1 exacerbations during the 0-to-24 and 24-to-48 month follow-ups. Having ≥1 exacerbation during baseline was significantly associated with ≥1 exacerbation during the 0-to-24 month (P = 0.0085) and 24-to-48 month follow-ups (P=<0.0001). Objective 2 cohort (N = 431) baseline FEV1 was significantly lower in patients who had more exacerbations; however, decline in FEV1 from baseline was not significantly different between patients with 0, 1, and ≥2 exacerbations. In patients with more baseline exacerbations, FEV1 % predicted was significantly lower at baseline (P < 0.0001) and at 12 (P = 0.0002) and 24 month follow-ups (P < 0.0001). ConclusionsPatients with frequent bronchiectasis exacerbations may be more likely than those with less frequent exacerbations to experience disease progression based on future exacerbation frequency and lower FEV1 at baseline, although FEV1 decline may not differ by baseline exacerbation frequency.

Stronger Associations of Centrilobular Than Paraseptal Emphysema With Longitudinal Changes in Diffusing Capacity and Mortality in COPD

The factors associated with longitudinal changes in diffusing capacity remain unclear among patients with COPD. Centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are major emphysema subtypes that may have distinct clinical-physiological impacts in these patients. Are CLE and PSE differently associated with longitudinal changes in diffusing capacity and mortality in patients with COPD? This pooled analysis included 399 patients with COPD from two prospective observational COPD cohorts. CLE and PSE were visually assessed on CT scan according to the Fleischner Society statement. The diffusing capacity and transfer coefficient of the lung for carbon monoxide (Dlco and KCO) and FEV1 were evaluated at least annually over a 5-year period. Mortality was recorded over 10 years. Longitudinal changes in FEV1, Dlco, and KCO and mortality were compared between mild or less severe and moderate or more severe CLE and between present and absent PSE in each Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The Dlco and KCO decline was weakly associated with FEV1 and greater in GOLD stage 3 or higher than in GOLD stages 1 and 2. Furthermore, moderate or more severe CLE, but not present PSE, was associated with steeper declines in Dlco for GOLD stages 1 and 3 or higher and KCO for all GOLD stages independent of age, sex, height, and smoking history. The moderate or more severe CLE, but not present PSE, was associated with additional FEV1 decline and higher 10-year mortality among patients with GOLD stage 3 or higher. A CT scan finding of moderate or more severe CLE, but not PSE, was associated with a subsequent accelerated impairment in diffusing capacity and higher long-term mortality in severe GOLD stage among patients with COPD.

Long-term results of sirolimus treatment in lymphangioleiomyomatosis: a single referral centre experience

There are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV1 decline greater than − 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV1 slope over 5 years was − 0.14 (− 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, − 54.00 (− 71.60 to − 36.39) ml/year in the partial responder group and − 84.19 (− 113.5 to − 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis. In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16years of age. Methacholine bronchoprovocation was available in 127 and 79 children at 7 and 12years of age, respectively. Longitudinal changes in FEV1 , FVC, and FEV1 /FVC z-scores and methacholine PC20 were analyzed. 55% of the study cohort (N=122) were male, and 55% were Caucasian. During follow-up, longitudinal changes in z-scores for pre- and post-bronchodilator FEV1 (P<.0001) FVC (P<.0001) and FEV1 /FVC (P<.0001 for pre- and 0.007 for post-bronchodilator) from age 5 to 10-16years were observed. Declined lung function in late childhood was significantly associated with gender, physician diagnosis of asthma, and allergic sensitization. PC20 geometric mean increased from 0.28mg/mL at 7years to 0.53mg/mL at 12years of age, and the frequency of abnormal bronchial hyperreactivity decreased from 96% to 78% (P=.0003). Following severe RSV bronchiolitis, there appear to be significant longitudinal changes in pre- and post-bronchodilator lung function during childhood. The study has several limitations including significant dropouts and the lack of a control group and post-bronchodilator measurements. Bronchial hyperreactivity is common in children following severe RSV bronchiolitis; however, it appears to decrease as they enter late childhood.

Progressive effects of single-nucleotide polymorphisms on 16 phenotypic traits based on longitudinal data

BackgroundThere are many research studies have estimated the heritability of phenotypic traits, but few have considered longitudinal changes in several phenotypic traits together.ObjectiveTo evaluate the progressive effect of single nucleotide polymorphisms (SNPs) on prominent health-related phenotypic traits by determining SNP-based heritability (h_{snp}^{2}) using longitudinal data.MethodsSixteen phenotypic traits associated with major health indices were observed biennially for 6843 individuals with 10-year follow-up in a Korean community-based cohort. Average SNP heritability and longitudinal changes in the total period were estimated using a two-stage model. Average and periodic differences for each subject were considered responses to estimate SNP heritability. Furthermore, a genome-wide association study (GWAS) was performed for significant SNPs.ResultsEach SNP heritability for the phenotypic mean of all sixteen traits through 6 periods (baseline and five follow-ups) were significant. Gradually, the forced vital capacity in one second (FEV1) reflected the only significant SNP heritability among longitudinal changes at a false discovery rate (FDR)-adjusted 0.05 significance level (h_{snp}^{2} = 0.171, FDR = 0.0012). On estimating chromosomal heritability, chromosome 2 displayed the highest heritability upon periodic changes in FEV1. SNPs including rs2272402 and rs7209788 displayed a genome-wide significant association with longitudinal changes in FEV1 (P = 1.22 × 10−8 for rs2272402 and P = 3.36 × 10−7 for rs7209788). De novo variants including rs4922117 (near LPL, P = 2.13 × 10−15) of log-transformed high-density lipoprotein (HDL) ratios and rs2335418 (near HMGCR, P = 3.2 times 10−9) of low-density lipoprotein were detected on GWAS.ConclusionSignificant genetic effects on longitudinal changes in FEV1 among the middle-aged general population and chromosome 2 account for most of the genetic variance.

COPD assessment test as a possible tool for evaluating health-related quality of life in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease that causes an obstructive ventilatory impairment similar to chronic obstructive pulmonary disease (COPD) and impairs the health-related quality of life (HRQoL). Here, we extended the use of the COPD assessment test (CAT) to patients with chronic respiratory diseases other than COPD. Specifically, the CAT was administered to patients with LAM for the first time. Using data from 25 patients with LAM at Juntendo University who participated in the Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety (MLSTS), we evaluated changes in pulmonary function, responses to HRQoL questionnaires (the CAT, St. George׳s Respiratory Questionnaire [SGRQ], EuroQOL Visual Analogue Scale [EuroQOL-VAS], and Functional Performance Inventory [FPI]), and the association between pulmonary function and HRQoL during a 24-month period of sirolimus treatment. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and CAT total scores improved over the 24 months of sirolimus treatment (5.33 ± 1.20 ml/month, 2.61 ± 1.16 ml/month, and -0.127 ± 0.022 score/month, respectively), whereas SGRQ total score, EuroQOL-VAS score, and FPI score did not. Most pulmonary functions at baseline were associated with the CAT breathlessness score during the first year. Longitudinal changes in FEV1, FEV1%predicted, or FEV1/FVC correlated significantly with the scores of CAT total, CAT breathlessness, and SGRQ activity. When analyzed by stepwise multivariate regression within a linear mixed-effects model, CAT breathlessness and confidence scores were significantly associated with a change in FEV1 from the baseline value (P = 0.0011, and P = 0.0441). Our results suggest that the CAT is a useful instrument for assessing HRQoL in sirolimus-treated patients with LAM.

Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

BackgroundGenome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined.ObjectivesWe aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline.MethodsWe analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12 695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts.ResultsThe 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10−16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts.ConclusionsPreviously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.

Differences in hyperpolarized (3) He ventilation imaging after 4 years in adults with cystic fibrosis.

To evaluate cystic fibrosis (CF) subjects over 4 years using (3) He magnetic resonance imaging (MRI), pulmonary function tests, and track hospitalization and physician visits. Five CF adults provided written informed consent to an approved protocol and underwent MRI, spirometry, and plethysmography at baseline, 7 days, and 4 ± 1 years later. (3) He MRI ventilation defect percent (VDP) was generated for all subjects and timepoints. After 4 years, mean forced expiratory volume in 1 second / forced vital capacity (FEV1 /FVC) was lower (P = 0.01) in all subjects and there were no other pulmonary function test changes. Two CF adults showed significantly elevated (worse) (3) He VDP at baseline and after 4 years they had significantly greater (worsened) VDP (P = 0.02), without a significant FEV1 decline (P = 0.06) but with a greater number of exacerbations (P < 0.05). Baseline VDP strongly correlated with FEV1 (r(2) = 0.98, P = 0.0007) at 4-year follow-up. For two CF subjects, VDP was significantly worse at baseline and worsened over 4 years, which was in agreement with a greater number of hospitalizations and clinic visits. These results are limited by the very small sample size, but the strong VDP correlation with longitudinal changes in FEV1 generates the hypothesis that abnormal VDP may temporally precede FEV1 decline in CF subjects; this must be tested in a larger CF study.

Cross-shift and longitudinal changes in FEV1 among wood dust exposed workers

ObjectivesAcute lung function (LF) changes might predict an accelerated decline in LF. In this study, we investigated the association between cross-shift and longitudinal changes in forced expiratory volume in 1...

S159 Do occupational asthmatics with small changes in PEF at work have less FEV1 decline than those with larger changes?

BackgroundThe significance of consistent small changes in PEF related to work, or records with diurnal variation within the normal range, are disputed. We related PEF changes at diagnosis to longitudinal...

Longitudinal relationship among growth, nutritional status, and pulmonary function in children with cystic fibrosis: Analysis of the Cystic Fibrosis Foundation National CF Patient Registry

Objective: To determine prospectively the relationship among growth, nutritional status, and pulmonary function over a 4-year period in a large cohort of children with cystic fibrosis (CF). Study design: CF Foundation National CF Patient Registry data collected from 1991 to 1995 for 968 children (507 male) aged 5 to 8 years with pancreatic insufficiency and forced expiratory volume in 1 second within 60% to 140% of predicted values (FEV1%) were analyzed longitudinally. Variables hypothesized to affect FEV1% included age, sex, z scores for height, weight, percent of height-appropriate body weight, and annual number of days hospitalized. Results: The significant decline in FEV1% was curvilinear and dependent on baseline FEV1%; children with initial FEV1% ≥90 declined 2.6 U/y more than those with initial FEV1% <90. Boys gained but girls declined in z scores for height. Girls decreased in z scores for weight at a greater rate than boys. The z scores for weight and percent of height-appropriate body weight were significantly associated with longitudinal changes in FEV1%, after adjustment was done for hospitalizations. Conclusions: Growth, nutritional status, and pulmonary function are not stable in prepubertal children with CF and pancreatic insufficiency. Important sex-related differences in growth occur before puberty. Growth and nutritional status are associated with changes in FEV1%, suggesting that nutritional intervention may slow the decline in pulmonary function in children with CF. (J Pediatr 2000;137:374-80)

Longitudinal changes in forced expiratory volume in one second in adults. Effects of smoking and smoking cessation.

Longitudinal changes in FEV1 (delta FEV1) in relationship to smoking habits were examined in 1,705 adults enrolled in a prospective study of a general population sample. In both men and women, there were excessive rates of decline in FEV1 in smokers, at least in those smoking more than 10 cigarettes per day. The excess decline of smokers was age dependent, particularly in men, with much of the excess loss of function occurring between 50 and 70 yr of age. Effects of smoking on delta FEV1, observed minus expected delta FEV1 and observed minus expected percent delta FEV1, were greater in men than in women even when controlled for current cigarette dose. Ex-smokers show delta FEV1 values similar to those of nonsmokers. In subjects younger than 35 yr of age, quitting smoking during follow-up was associated with an actual increase in FEV1. In men 50 to 70 yr of age, smoking cessation early in the study appeared to lead to a relatively prompt return to normal rates of functional decline. Thus, the findings suggest relatively prompt beneficial effect of smoking cessation even in late middle age.

Longitudinal changes in forced expiratory volume in one second in adults. Methodologic considerations and findings in healthy nonsmokers.

Longitudinal changes in FEV1 (delta FEV1) have been examined in a sample of the general population of Tucson, Arizona. Adults with satisfactory spirometric tests in all 7 surveys performed over a period of 11 yr showed some between-survey differences in mean FEV1. Although small in absolute magnitude, such survey biases (which would be impossible to detect unless multiple spirometric tests were carried out on a relatively large group of subjects) could have a marked effect on calculated changes in FEV1 and may explain the widely divergent delta FEV1 values reported in the literature. After adjusting for survey biases, the relationships of delta FEV1 to age, sex, and body size were examined in "healthy" nonsmokers in the population who were followed for an average of 9.6 yr. The FEV1 showed an accelerating decline with age, and delta FEV1 was best explained by a model of proportional change in which it is a function of Age X Height3. Longitudinally determined delta FEV1 showed much less decline in function and a later apparent age of onset of decline than suggested by cross-sectional analyses. While small "learning effects" in longitudinal calculations cannot be excluded, most of the cross-sectional versus longitudinal differences are probably ascribable to past events that have adversely affected the FEV1 in older adults, thereby increasing cross-sectional age effects. Present findings also suggest that generally applicable "prediction equations" for delta FEV1 probably cannot be developed and that delta FEV1 values should only be compared between groups studied in an identical manner within a given study.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary function in firefighters: a six-year follow-up in the Boston Fire Department.

Tests of ventilatory capacity, objective cough, and standardized respiratory questionnaires were used in a prospective study to measure the effect of firefighting on pulmonary function in a cohort of 951 white Boston firefighters between 1970-1976. During the six years of follow-up, the mean annual decrements in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were 36 and 29 ml per year, respectively. At the end of the study in 1976, the mean FEV1 for this group was 98.3% of the level predicted for healthy nonsmoking adults, while the FVC was 97.8%. Current cigarette smoking was associated with an increased prevalence of bronchitis, a loose cough, reduced levels of FEV1 and FVC, and increased longitudinal changes in FEV1 and FVC. The longitudinal changes and current levels of FEV1 and FVC were not correlated with any index of firefighting exposure in active firefighters. Increased use of protective respiratory apparatus and previously described selection effects within the Boston Fire Department appear to be protecting this group of firefighters from long-term effects of smoke exposure as measured by these techniques.