Annual Lung Function Decline Research Articles

Prevalence and Outcomes of Achromobacter Species Infections in Adults with Cystic Fibrosis: a North American Cohort Study.

Achromobacter species are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian adult CF clinic who had positive sputum cultures for Achromobacter species in the period from 1984 to 2013. Infection was categorized as transient or persistent (≥50% positive cultures for 1 year). Those with persistent infection were matched 2:1 with age-, sex-, and time-matched controls without a history of Achromobacter infection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency and lung function decline. Isolates from a biobank were retrospectively assessed, identified to the species level by nrdA sequencing, and genotyped using pulsed-field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8 years), developed Achromobacter infection. Ten patients (29%) developed persistent infection. Persistence did not denote permanence, as most patients ultimately cleared infection, often after years. Patients were more likely to experience PEx at incident isolation than at prior or subsequent visits (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7]; P = 0.03). Following persistent infection, there was no difference in annual lung function decline (-1.08% [95% CI, -2.73 to 0.57%] versus -2.74% [95% CI, -4.02 to 1.46%]; P = 0.12) or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28]; P = 0.70). Differential virulence among Achromobacter species was not observed, and no cases of transmission occurred. We demonstrated that incident Achromobacter infection was associated with a greater risk of PEx; however, neither transient nor chronic infection was associated with a worsened long-term prognosis. Large, multicenter studies are needed to clarify the clinical impact, natural history, and transmissibility of Achromobacter.

Effect of a single exacerbation on decline in lung function in COPD

BackgroundCOPD exacerbations are associated with accelerated lung function decline, but whether they are causal is unknown. We evaluated the effect of a single exacerbation on rate of lung function change using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial. MethodsRetrospective analysis of annual rates of decline in FEV1 and FVC before and after a single (and the only) moderate-to-severe exacerbation in patients during UPLIFT® (exacerbator subgroup), compared with changes between the first and second half of the study in a non-exacerbator subgroup. A sensitivity analysis examined annual rates of decline in matched pairs of exacerbators and non-exacerbators. ResultsFollowing the single moderate-to-severe exacerbation, mean annual decline in post-bronchodilator lung function increased compared with the rate of decline before the exacerbation (FEV1 76.5 vs. 39.1 mL/year, p = 0.003; FVC 106.5 vs. 34.7 mL/year, p = 0.011). In non-exacerbators, there were no differences in rates of decline between the first and second halves of the study (post-bronchodilator FEV1 38.2 vs. 41.8 mL/year, FVC 45.3 vs. 43.9 mL/year. Before the single (moderate-to-severe) exacerbation in the exacerbator subgroup, declines in post-bronchodilator FEV1 or FVC were similar to non-exacerbators in the first half of the study; after the single exacerbation they were significantly higher than for non-exacerbators in the second half of the study. The sensitivity analysis showed similar results. ConclusionA single COPD exacerbation may result in significant increase in the rate of decline in lung function.

The Effects of Pleural Plaques on Longitudinal Lung Function in Vermiculite Miners of Libby, Montana

BackgroundThis study was conducted to assess associations of pleural plaques (PP) and longitudinal lung function in vermiculite miners of Libby, Montana who are occupationally exposed to asbestos. High-resolution computed tomography (HRCT) was used to identify asbestos-related findings in former Libby vermiculite miners. We investigated annual lung function decline in miners with PP only and compared them to miners with normal HRCT findings. Materials and MethodsHRCTs from 128 miners were categorized into the following 4 diagnostic groups: (1) normal computed tomography scan (n = 9); (2) PP only (n = 72); (3) PP and interstitial fibrosis (n = 26) and (4) additional HRCT abnormalities (n = 21) such as rounded atelectasis, diffuse pleural thickening, pleural effusions or pulmonary nodules or tumor >1cm in diameter. Random intercept and slope linear mixed-effect regression models identified differences in lung function decline between miners with asbestos-associated outcomes and those with normal HRCT. Models were adjusted for follow-up time, body mass index, smoking status, latent exposure period and employment years. Interactions for smoking status with age and smoking status with pleural plaque severity were examined. ResultsMiners with PP only did not have an accelerated decline in lung function between 40 and 80 years. Miners with PP and additional HRCT abnormalities displayed significantly accelerated declines in forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide (P = 0.05 and P < 0.01, respectively). Plaque severity did not affect lung function decline. However, smokers with extensive plaques displayed accelerated loss in diffusing capacity of the lungs for carbon monoxide and forced expiratory volume in 1 second when compared to nonsmoking miners with mild plaque formation. ConclusionsPP alone did not significantly affect lung function decline in vermiculite miners of Libby, Montana.

Determinants of annual change in physical activity in COPD.

Daily physical activity (PA) is reduced in patients with COPD. Previous cross-sectional analyses indicate various predictors for a low level of PA including airway obstruction, exacerbations and co-morbidities. However, information from longitudinal studies evaluating PA in the context of disease progression, survival and co-morbidities is scant. In a heterogeneous cohort of COPD patients, we annually assessed the number of steps per day over 1 week and potential determinants including lung function, exacerbations and co-morbidities. Univariable and multivariable mixed effect models were used to investigate associations between the change in steps per day (dependent variable) and possible predictors and their annual changes. A total of 177 COPD patients (46% GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 1/2, 38% stage 3 and 16% stage 4) with a mean (min/max) follow-up time of 2.7 (1/5) years were annually assessed. The number of steps per day decreased significantly over time (P < 0.001) with a mean annual change of -508 steps. The decrease in activity was significantly associated with forced expiratory volume in 1 s (FEV1 ) % predicted (P = 0.020) but not with annual changes in FEV1 . Hyperinflation, exacerbations, co-morbidities and their annual changes, and survival did not significantly affect change in PA. COPD patients have a substantial decrease of PA over time. This decrease seems to be determined by the degree of airflow limitation. However, patients with a greater annual decline in lung function did not show a greater decrease in PA. The rate of decline in PA did not differ between survivors and non-survivors in this cohort.

External Validation of Health Economic Decision Models for Chronic Obstructive Pulmonary Disease (COPD): Report of the Third COPD Modeling Meeting.

To validate outcomes of presently available chronic obstructive pulmonary disease (COPD) cost-effectiveness models against results of two large COPD trials-the 3-year TOwards a Revolution in COPD Health (TORCH) trial and the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial. Participating COPD modeling groups simulated the outcomes for the placebo-treated groups of the TORCH and UPLIFT trials using baseline characteristics of the trial populations as input. Groups then simulated treatment effectiveness by using relative reductions in annual decline in lung function and exacerbation frequency observed in the most intensively treated group compared with placebo as input for the models. Main outcomes were (change in) total/severe exacerbations and mortality. Furthermore, the absolute differences in total exacerbations and quality-adjusted life-years (QALYs) were used to approximate the cost per exacerbation avoided and the cost per QALY gained. Of the six participating models, three models reported higher total exacerbation rates than observed in the TORCH trial (1.13/patient-year) (models: 1.22-1.48). Four models reported higher rates than observed in the UPLIFT trial (0.85/patient-year) (models: 1.13-1.52). Two models reported higher mortality rates than in the TORCH trial (15.2%) (models: 20.0% and 30.6%) and the UPLIFT trial (16.3%) (models: 24.8% and 36.0%), whereas one model reported lower rates (9.8% and 12.1%, respectively). Simulation of treatment effectiveness showed that the absolute reduction in total exacerbations, the gain in QALYs, and the cost-effectiveness ratios did not differ from the trials, except for one model. Although most of the participating COPD cost-effectiveness models reported higher total exacerbation rates than observed in the trials, estimates of the absolute treatment effect and cost-effectiveness ratios do not seem different from the trials in most models.

Physical activity and lung function decline in adults with asthma: The HUNT Study.

People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. The mean decline in forced expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)). The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: -2 mL/year (95% CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: -0.14%/year (95% CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: -4 mL/year (95% CI: -9 to 1)). We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

Insights from the German Compassionate Use Program of Nintedanib for the Treatment of Idiopathic Pulmonary Fibrosis

Background: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and has been shown to slow disease progression by reducing annual lung function decline. Objective: To evaluate the results of a large cohort of IPF patients treated with nintedanib within a compassionate use program (CUP) in Germany (9 centers). Methods: Patients (≥40 years) were required to have a confirmed diagnosis of IPF, a forced vital capacity (FVC) ≥50% predicted (pred.) and a carbon monoxide diffusing capacity (D<smlcap>LCO</smlcap>) 30-79% pred. and not to be eligible for pirfenidone treatment. Clinical data, pulmonary function tests and adverse events were recorded up to July 2015. Results: Sixty-two patients (48 male/14 female) with moderate IPF (FVC 64 ± 17% pred. and D<smlcap>LCO</smlcap> 40 ± 10% pred.) were treated with nintedanib. 77% of patients switched from pirfenidone (mean treatment duration 14 ± 2 months) mostly due to disease progression (mean decline in FVC 7.4 ± 3% pred. in the 6 months prior to nintedanib intake). Initiation of nintedanib treatment occurred 69 ± 29 months after IPF diagnosis, and mean treatment duration was 8 ± 4 months. Most patients (63%) stabilized 6 months after treatment start (mean FVC decline 3 ± 1 vs. -17 ± 2% in patients with disease progression; p < 0.01). The most common adverse events were diarrhea (63%) and weight loss (50%). Dose reduction occurred in 34% of cases and treatment discontinuation in 10%. Conclusion: Nintedanib treatment was generally well tolerated and was associated with FVC stabilization in the majority of IPF patients in this CUP setting where most patients were not treatment naïve. Our data are in agreement with the previously published data.

Impact of Long-Term Tiotropium Bromide Therapy on Annual Lung Function Decline in Adult Patients with Cystic Fibrosis.

BackgroundChronic lung disease is the leading cause of death in patients with Cystic Fibrosis (CF) and is often treated with bronchodilators. It is not known whether long-term tiotropium bromide treatment may have a positive impact on lung function.MethodsThis retrospective cohort study estimated annual lung function decline utilizing longitudinal data for forced expiratory volume in 1 s (FEV1).ResultsA total of 160 adult patients with CF were analyzed. The subjects treated for 24 months with tiotropium bromide had a significantly slower decline of mean annual change of FEV1 (treated: -0.3±4.0%; control: -2.3±5.0%; p = 0.0130). In patients with FEV1 ≥70% predicted, long-term tiotropium bromide treatment was associated with greater improvements in annual lung function decline (FEV1 ≥70% predicted: treated: +0.5±4.7%; control: -4.0±6.3%; p = 0.0132; FEV1 50–69% predicted: treated: -0.5±4.4%; control: -0.8±3.8%; p = 0.7142; FEV1 ≤49% predicted: treated: -0.6±3.4%; control: -2.4±4.8%; p = 0.0898).ConclusionThis study suggests that long-term tiotropium bromide treatment may be associated with reduced annual decline of FEV1 in patients with CF, particularly in adults with a mild degree of severity.

Annual decline in forced expiratory volume is steeper in aluminum potroom workers than in workers without exposure to potroom fumes.

BackgroundAluminum potroom exposure is associated with increased mortality of COPD but the association between potroom exposure and annual decline in lung function is unknown. We have measured lung volumes annually using spirometry from 1986 to 1996. The objective was to compare annual decline in forced expiratory volume in 1 s (dFEV1) and forced vital capacity (dFVC).MethodsThe number of aluminum potroom workers was 4,546 (81% males) and the number of workers in the reference group was 651 (76% males). The number of spirometries in the index group and the references were 24,060 and 2,243, respectively.ResultsAfter adjustment for confounders, the difference in dFEV1 and dFVC between the index and reference groups were 13.5 (P < 0.001) and −8.0 (P = 0.060) ml/year.ConclusionAluminum potroom operators have increased annual decline in FEV1 relative to a comparable group with non‐exposure to potroom fumes and gases. Am. J. Ind. Med. 59:322–329, 2016. © 2016 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc.

Association of incidental emphysema with annual lung function decline and future development of airflow limitation.

ObjectivesEmphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities.Materials and methodsSubjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below −950 Hounsfield units (%LAA−950) was calculated automatically. A calculated value of %LAA−950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models.ResultsA total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (−33.9 versus −18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up.ConclusionIncidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed.

Prognostic Value of the Six-Second Spirometry in Patients with Chronic Obstructive Pulmonary Disease: A Cohort Study.

BackgroundThe six-second spirometry has been proposed as an alternative to diagnose airflow limitation, although its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unknown. The purpose of this study was to determine the prognostic value of the postbronchodilator forced expiratory volume in 1 second (FEV1)/forced expiratory volume in 6 seconds (FEV6) ratio and FEV6 in COPD patients.Methods and FindingsThe study population consisted of 2,614 consecutive stable patients with COPD. The patients were monitored for an average period of 4.3 years regarding mortality, hospitalizations by COPD exacerbations, diagnosis of lung cancer, and annual lung function decline. The overall rate of death was 10.7 (95%CI: 8.7–12.7) per 1000 person-years. In addition to male gender, age and comorbidity, FEV6 (hazard ratio [HR]: 0.981, 95%CI: 0.968–0.003) and FEV1/FEV6 quartiles (lowest quartile (<74% pred.): HR 3.558, 95%CI: 1.752–7.224; and second quartile (74–84% pred.): HR 2.599, 95%CI: 1.215–5.561; versus best quartile (>0.89% pred.)) were independently associated with mortality, whereas FEV1 was not retained in the model. 809 patients (30.9%) had at least one hospital admission due to COPD exacerbation. In addition to sex, age, smoking and comorbidity, FEV1 and FEV1/FEV6 quartiles were independent risk factors of hospitalization. FEV6 was the only spirometric parameter independently related with lung function annual decline, while the FEV6 and FEV1/FEV6 quartiles were independent risk factors for lung cancer.ConclusionsIn a general COPD outpatient population, airflow obstruction assessed by the FEV1/FEV6 is an independent risk factor for both death and hospitalization.

Effect of tiotropium on lung function decline in early-stage of chronic obstructive pulmonary disease patients: propensity score-matched analysis of real-world data.

BackgroundTiotropium failed to slow the annual rate of forced expiratory volume in 1 second (FEV1) decline in chronic obstructive pulmonary disease (COPD) patients with <70% predicted FEV1. However, the rate of FEV1 decline is known to be faster at early stages, which suggests that the effects of tiotropium may be more prominent in early-stage of COPD patients. The aim of this study was to test the hypothesis that tiotropium modifies the rate of FEV1 decline in COPD patients with an FEV1≥70%.MethodsWe retrospectively reviewed the records of COPD patients diagnosed between January 1, 2004, and July 31, 2012, at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. The inclusion criteria were as follows: age ≥40 years, postbron-chodilator (BD) FEV1≥70% of predicted and FEV1/FVC (forced vital capacity) <0.70, and spirometry more than two times at certain times of the year. Conversely, the exclusion criteria were as follows: asthma, lung cancer, pulmonary tuberculosis, pulmonary resection, or long-term use of a short-acting muscarinic antagonist. The annual lung function decline in patients using tiotropium was compared with that in patients not using the drug.ResultsOf the 587 patients enrolled in the study, 257 took tiotropium. Following propensity score matching, 404 patients were included in the analysis. The mean annual rate of post-BD FEV1 decline was 23.9 (tiotropium) and 22.5 (control) mL/yr (P=0.86); corresponding pre-BD values were 30.4 and 21.9 mL/yr (P=0.31), respectively. Mean annual rate of post-BD FVC decline was 55.1 (tiotropium) and 43.5 (control) mL/yr (P=0.33); corresponding pre-BD values were 37.1 and 33.3 mL/yr (P=0.13).ConclusionTherefore, tiotropium does not reduce the rate of lung function decline in COPD patients with FEV1≥70%.

Achromobacter xylosoxidans infection in an adult cystic fibrosis unit in Madrid

BackgroundAchromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. MethodsA microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). ResultsA. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18–39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. ConclusionsA. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism.

Supplementing Defect in Club Cell Secretory Protein Attenuates Airway Inflammation in COPD

Club cell secretory protein (CCSP) is a protective biomarker associated with annual decline in lung function. COPD progression results from an imbalance between injury and repair initially triggered by cigarette smoking. We investigated the effect of CCSP as a therapeutic strategy to restore the balance between injury and repair in COPD simultaneously, validating an ex vivo air-liquid interface (ALI) culture of human bronchial epithelial cells. Endobronchial biopsy specimens (EBBs) were obtained from 13 patients with COPD, eight smokers, and eight control subjects. Morphometric analysis of the initial EBBs was performed. ALI cultures derived from the same EBBs were exposed to cigarette smoke extract (CSE) with or without exogenous recombinant human CCSP (rhCCSP) supplementation. CCSP and IL-8 concentrations were assessed at steady state and after CSE exposure. Morphometric analysis of the initial EBBs showed increased cell density but decreased immunostaining of CCSP+ cells in EBBs of patients with COPD (P = .03 vs control subjects). At steady state, lower CCSP (P = .04) and higher IL-8 levels (P < .0001) were found in COPD ALI epithelium. Exogenous rhCCSP supplementation dampened CSE-induced IL-8-release in patients with COPD and returned to levels similar to those of smokers and control subjects (P = .0001). A negative correlation was found between IL-8-release in ALI and CCSP+ cell density in initial biopsy specimens (P = .0073). In vitro, rhCCSP exogenous supplementation can reverse CSE-induced IL-8 release in biopsy specimens from patients with COPD, indicating a potential use of this strategy in vivo.

Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.

Background: Both air pollution and genetic variation have been shown to affect lung function. Their interaction has not been studied on a genome-wide scale to date.Objectives: We aimed to identify, in an agnostic fashion, genes that modify the association between long-term air pollution exposure and annual lung function decline in an adult population-based sample.Methods: A two-stage genome-wide interaction study was performed. The discovery (n = 763) and replication (n = 3,896) samples were derived from the multi-center SAPALDIA cohort (Swiss Cohort Study on Air Pollution and Lung Disease in Adults). Annual rate of decline in the forced mid-expiratory flow (FEF25–75%) was the main end point. Multivariate linear regression analyses were used to identify potential multiplicative interactions between genotypes and 11-year cumulative PM10 exposure.Results: We identified a cluster of variants intronic to the CDH13 gene as the only locus with genome-wide significant interactions. The strongest interaction was observed for rs2325934 (p = 8.8 × 10–10). Replication of the interaction between this CDH13 variant and cumulative PM10 exposure on annual decline in FEF25–75% was successful (p = 0.008). The interaction was not sensitive to adjustment for smoking or body weight.Conclusions: CDH13 is functionally linked to the adipokine adiponectin, an inflammatory regulator. Future studies need to confirm the interaction and assess how the result relates to previously observed interactions between air pollution and obesity on respiratory function.Citation: Imboden M, Kumar A, Curjuric I, Adam M, Thun GA, Haun M, Tsai MY, Pons M, Bettschart R, Turk A, Rochat T, Künzli N, Schindler C, Kronenberg F, Probst-Hensch NM. 2015. Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis. Environ Health Perspect 123:72–79; http://dx.doi.org/10.1289/ehp.1307398

Five-Year Lung Function Observations and Associations With a Smoking Ban Among Healthy Miners at High Altitude (4000 m)

To assess the annual lung function decline associated with the reduction of secondhand smoke exposure in a high-altitude industrial workforce. We performed pulmonary function tests annually among 109 high-altitude gold-mine workers over 5 years of follow-up. The first 3 years included greater likelihood of exposure to secondhand smoke exposure before the initiation of extensive smoking restrictions that came into force in the last 2 years of observation. In repeated measures modeling, taking into account the time elapsed in relation to the smoking ban, there was a 115 ± 9 (standard error) mL per annum decline in lung function before the ban, but a 178 ± 20 (standard error) mL per annum increase afterward (P < 0.001, both slopes). Institution of a workplace smoking ban at high altitude may be beneficial in terms of lung function decline.

Chronic Productive Cough is Associated with Death in Smokers with Early COPD

Cough and phlegm are common in COPD. Previous studies have shown conflicting evidence regarding their association with mortality and lung function. We sought to better understand how cough and phlegm impact mortality and lung function in COPD. We analyzed data from the Lung Health Study, consisting of 5,887 smokers with mild to moderate airflow obstruction followed longitudinally. We assessed the association between baseline symptoms of cough alone, phlegm alone, and cough and phlegm with 12.5-year mortality and annual lung function decline. Average age at entry was 48.5 years (± 6.8) with 63% males and 4% African Americans. Cough alone was present in 17%, phlegm alone in 12%, while 31% had both. Neither symptom alone was associated with death, but the combination was associated with increased risk of death after adjustment for age, gender, race, smoking status at year 5, pack-years smoked, randomization group, baseline FEV1 percent predicted (HR 1.27, 95% CI 1.02–1.59). Individuals with cough and phlegm together more commonly died of respiratory causes than those without. Cough with phlegm was associated with 48 mL lower baseline FEV1 (95% CI –90, –6), while neither symptom alone was associated with baseline FEV1. No symptom was associated with FEV1 longitudinally. Cough and phlegm together are associated with mortality and lung function decrement in mild-to-moderate COPD, independent of lung function and smoking status. Respiratory causes of death are common among those with cough and phlegm. Such information can help to identify subsets of individuals with COPD having higher risk for adverse outcomes.

410 Estimating the burden of occupational Chronic Obstructive Pulmonary Disease (COPD) in the UK

ObjectiveAs part of a UK Biobank project to investigate the causes of COPD in the UK, initial estimates have been made of the burden of COPD attributed to occupational exposures,...

The effect of HIV infection on longitudinal lung function decline among IDUs

As survival with HIV infection improves, HIV-infected individuals appear to be susceptible to development of chronic diseases, including restrictive and obstructive lung diseases. We sought to determine the independent association of HIV infection on lung function decline. Longitudinal analysis of the AIDS Linked to the Intravenous Experience study, an observational cohort of current and former IDUs. Generalized estimating equations were used to determine the effects of markers of HIV infection on adjusted annual change in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A total of 1064 participants contributed 4555 spirometry measurements over a median follow-up time of 2.75 years. The mean age of the cohort was 48 years; nearly, two-thirds were men and 85% current smokers. After adjustment, the overall annual decline of FEV1 and FVC between HIV-infected and uninfected persons did not differ. However, there was a 76 ml/year greater rate of decline in FEV1 and 86 ml/year greater rate of decline in FVC among HIV-infected participants with viral load more than 75 000 copies/ml compared with HIV-uninfected individuals (P < 0.01). Similarly, HIV-infected individuals with CD4 cell count less than 100 cells/μl had a 57 ml/year more rapid decline in FEV1 and 86 ml/year more rapid decline in FVC than HIV-uninfected participants (P = 0.018 and P = 0.001, respectively). Markers of poorly controlled HIV disease are independently associated with accelerated annual lung function decline, with decrements in both FEV1 and FVC. These findings highlight the need for optimized HIV antiretroviral therapy in addition to smoking cessation among HIV-infected individuals with tobacco dependence.

Air Pollution Irreversibly Impairs Lung Function: A Twenty-Year Follow-Up of Officially Acknowledged Victims in Japan

Lung function is one of the strongest determinants of cardiopulmonary health and longevity. Long-term exposure to air pollution has been associated with decreased lung function. We undertook a retrospective study to compare the long-term consequences of air pollution in two areas of Japan: Mizushima, Okayama Prefecture and Kitakyushu, Fukuoka Prefecture. Industrialization began in Mizushima in the 1940s, whereas it began in Kitakyushu in the early 1900s. In Kitakyushu, levels of nitrogen dioxide have been higher compared to the Mizushima area. The subjects comprised 623 officially acknowledged victims of pollution-related illness (489 from Mizushima and 134 from Kitakyushu). All subjects were lifetime non-smokers and aged 65 years or older at the time of their last medical examination in 2009. Demographic data including diagnosed lung diseases and lung function at the time of certification assessment performed between 1973 and 1988 were obtained. The subjects from Kitakyushu were significantly younger (47.1 vs. 51.0 years, p < 0.001) and a higher percentage had asthma (91.2 vs. 36.8%, p < 0.001) compared to those from Mizushima. Furthermore, all measures of lung function were significantly lower in Kitakyushu group at the time of the certification assessment (p < 0.001) and at the follow-up (p < 0.001). However, no significant differences were observed in the annual mean decline in lung function between the two groups, despite the overall decrease in air pollution. In conclusion, the normal lung function is not restored even after improvement of air pollution. It is essential for every city to prevent air pollution.