Rapid Decline In Pulmonary Function Research Articles

Association Between Decreased Renal Function and Pulmonary Function Decline in Community-dwelling Adults.

Emerging evidence suggests that there is a close relationship between the human lung and kidney. This study evaluated whether decreased renal function was associated with accelerated pulmonary function decline in a large-scale community-based cohort. A total of 10,028 subjects of the prospective Ansung-Ansan cohort were eligible for the longitudinal analysis of changes in pulmonary function associated with decreased renal function (glomerular filtration rate <60 ml/min/1.73 m2). Logistic regression analysis was performed to evaluate factors associated with decreased baseline renal function, and a linear mixed model compared changes in pulmonary function in participants with and without decreased renal function after propensity score matching (PSM). At baseline, subjects with and without decreased renal function showed distinct characteristics, and the factors associated with decreased renal function were age, baseline forced vital capacity, hypertension, and white blood cell (WBC) count. A 1:4 PSM of age, sex, body mass index, and smoking status showed that the proportion of those with hypertension and the WBC count differed between the patients with decreased and normal renal function. In the PSM population, those with decreased renal function had a greater decline in forced expiratory volume in the first second (FEV1) than those without (p=0.0402); however, these differences were not found to be evident when hypertension and WBC count were further matched (p=0.0807). The results of our study demonstrated that decreased renal function was not directly associated with the rapid decline in pulmonary function in a community-based general population setting.

Lung Transplantation for COVID-19 Acute Respiratory Distress Syndrome: The British Columbian Experience With New Disease Pathology

Lung transplantation is a life-saving treatment for patients with end-stage lung disease. COVID-19 has been associated with a severe and rapid decline in pulmonary function, in which case lung transplantation has been described to be effective. We herein describe 9 patients who underwent lung transplantation for COVID-19 acute respiratory distress syndrome, of whom 6 were bridged with extracorporeal membrane oxygenation (ECMO). The median time of pre-operative observation periods was 54 days to ensure no lung function recovery and the time to wean off extracorporeal membrane oxygenation was 3 days. Patients had comparable short-term survival outcomes to non-COVID-19 lung transplant recipients at our institution during the same time period. Lung transplantation for COVID-19-associated lung disease is feasible with comparable short-term outcomes and may liberate patients from extracorporeal supports.

AB0697 Dramatic reduction of mortality rate by tofacitinib in anti-MDA-5 antibody-positive patients with rapidly progressive interstitial lung disease

BackgroundRapidly progressive interstitial lung disease (RP-ILD) is often seen in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody. They often have a poor prognosis with rapid decline in pulmonary function, leading to respiratory failure (1). Aggressive immunosuppressive therapy has been reported with improved prognosis, however; it may lead to opportunistic infections, including cytomegalovirus (CMV) or Pneumocystis pneumonia (PCP) infection (2, 3).ObjectivesThis study aimed to evaluate the effectiveness of tofacitinib (TOF) in combination with CMV and PCP prophylaxis in anti-MDA-5-positive patients.MethodsMedical records of 17 anti-MDA-5-positive RP-ILD patients enrolled during Mar 2017 to May 2021 were reviewed. RP-ILD was defined by the presence of deteriorated dyspnea, with a decrease in PaO2 levels and emerging radiographic anomalies within 4 weeks without evidence of infection (4). Chest CT was scored using Ichikado score (5). Clinical parameters including ferritin levels, white counts (WBC), Lactate dehydrogenase (LDH) levels, GAP scores (Gender, Age, and Physiology score for idiopathic pulmonary fibrosis) were recorded. Medications included cyclophosphamide (CyP), intravenous immunoglobulin (IVIG), mycophenolic acid derivatives (MPA), rituximab (RTX), and calcineurin inhibitor (CNI). Kaplan-Meier survival analysis and Log-rank test were used to evaluate one-year mortality differences (MedCalc version 19.6). The Ethics Committee approved our study (CE17038B).ResultsSix anti-MDA-5-positive RP-ILD patients were treated with tofacitinib; five had concomitant CMV prophylaxis with valganciclovir (VGCV); 4 had PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMX). Patients’ demographic data are shown in Table 1. The median age, clinical manifestations, laboratory data, and chest CT scores were comparable between tofacitinib and non-tofacitinib groups. Prevalence of MPA use was higher in the non-TOF group. Kaplan-Meier survival analysis (Figure 1) indicated that patients with tofacitinib treatment (p=0.001), valganciclovir (p=0.003), and TMP-SMX (p=0.028) prophylaxis exhibited better 1-year survival rates compared with those without TOF therapy, VGCV, and TMP-SMX prophylaxis.Table 1.Clinical characteristics of anti-MDA-5 antibody-positive patients with RP-ILD receiving tofacitinib vs non-tofacitinib treatment.Tofacitinib (n=6)Non-tofacitinib (n=11)p valueAge (years)58 (42.3-77)57 (50.0-62.0)0.884Female sex, n (%)2 (33.3)6 (54.5)0.620Diabetes mellitus, n (%)0 (0)5 (45.5)0.102Fever, n (%)5 (83.3)10 (90.9)1.000Mechanic’s hands, n (%)4 (66.7)5 (45.5)0.620Ferritin (n=16, ng/ml))2670.9 (719.7-4209.7)1563.5 (967.8-3169.0)0.635WBC (x1000μl)8.7 (6.5-9.9)8.7 (6.0-12.9)0.884LDH (n=16, U/l)367.0 (218.0-557.5)433.0 (331.0-625.3)0.313GAP score5 (2.5-8)5 (2-6)0.808CT score200.0 (124.2-214.2)196.7 (153.3-273.3)0.733TMP-SMX, n (%)4 (66.7)0 (0)0.006**VGCV, n (%)5 (83.3)0 (0)0.001**CyP, n (%)1 (16.7)4 (36.4)0.600IVIG, n (%)1 (16.7)6 (54.5)0.304MPA, n (%)0 (0)7 (63.6)0.035*RTX, n (%)3 (50.0)5 (45.5)1.000CNI, n (%)2 (33.3)6 (54.5)0.620Continuous variables were expressed as median (inter-quartile range).*p&lt;0.05, **p&lt;0.01 by Mann–Whitney U test or Fisher’s Exact test.Figure 1.ConclusionThe study demonstrated the efficacy of tofacitinib treatment in anti-MDA-5-positive RP-ILD. In addition, CMV and PCP prophylaxis appeared to improve in 1-year survival. Rheumatologists might consider TOF with prophylaxis as an option for anti-MDA-5-positive patients in daily practice.

Developing Pulmonary Rehabilitation for COVID-19: Are We Linked with the Present Literature? A Lexical and Geographical Evaluation Study Based on the Graph Theory.

The Coronavirus Disease 2019 (COVID-19) pandemic is a severe ongoing global emergency. Despite high rates of asymptomatic patients, in many cases, the infection causes a rapid decline in pulmonary function due to an acute respiratory distress-like syndrome, leading to multi-organ failure and death. To date, recommendations about rehabilitation on COVID-19 are based on clinical data derived from other similar lung diseases. Rehabilitation literature lacks a standard taxonomy, limiting a proper evaluation of the most effective treatments for patients after COVID-19 infection. In this study, we assessed the clinical and rehabilitative associations and the geographical area involved in interstitial lung diseases (ILD) and in COVID-19, by a mathematical analysis based on graph theory. We performed a quantitative analysis of the literature in terms of lexical analysis and on how words are connected to each other. Despite a large difference in timeframe (throughout the last 23 years for ILD and in the last 1.5 years for COVID-19), the numbers of papers included in this study were similar. Our results show a clear discrepancy between rehabilitation proposed for COVID-19 and ILD. In ILD, the term “rehabilitation” and other related words such as “exercise” and “program” resulted in lower values of centrality and higher values of eccentricity, meaning relatively less importance of the training during the process of care in rehabilitation of patients with ILD. Conversely, “rehabilitation” was one of the most cited terms in COVID-19 literature, strongly associated with terms such as “exercise”, “physical”, and “program”, entailing a multidimensional approach of the rehabilitation for these patients. This could also be due to the widespread studies conducted on rehabilitation on COVID-19, with Chinese and Italian researchers more involved. The assessment of the terms used for the description of the rehabilitation may help to program shared rehabilitation knowledge and avoid literature misunderstandings.

Scleroderma-associated interstitial lung disease – new therapeutic approach

Scleroderma is a systematic autoimmune disease characterized by endothelial dysfunction which causes small vessel disease, fibroblastic disorder with excessive production of collagen and fibrosis, as well as immunological disorders. Direct lung damage leading to interstitial lung disease is developed early after diagnosis. The result is a rapid decline in pulmonary function with worsening of quality of life and severe disability in these patients. The purpose of this review is to present all known medicaments for treatment of patients with scleroderma-associated interstitial lung disease – not only approved, but also those still being researched. Modern tendencies require the therapy to be guided by both rheumatologists and pulmonologists, as well as the participation of highly qualified radiologists. Correct clinical approach will enable the achievement of maximum results aimed at improving the quality of life and its duration in this group of patients.

Thymus and activation-regulated chemokine (TARC/CCL17) predicts decline of pulmonary function in patients with chronic obstructive pulmonary disease

BackgroundThe deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. MethodsWe recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. ResultsIn the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. ConclusionsTARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.

Late-onset "acute fibrinous and organising pneumonia" impairs long-term lung allograft function and survival.

Acute fibrinous and organising pneumonia (AFOP) after lung transplantation is associated with a rapid decline in pulmonary function. However, the relation with chronic lung allograft dysfunction (CLAD) remains unclear. We investigated the association between detection of AFOP in lung allograft biopsies with clinically important endpoints.We reviewed lung allograft biopsies from 468 patients who underwent lung transplantation at the University Hospitals Leuven (2011-2017). AFOP was categorised as early new-onset (≤90 days post-transplant) or late new-onset (>90 days post-transplant); and associated with CLAD-free survival, graft survival, donor-specific antibodies, airway and blood eosinophilia.Early and late AFOP was detected in 24 (5%) and 30 (6%) patients, respectively. CLAD-free survival was significantly lower in patients with late AFOP (median survival 2.42 years; p<0.0001) compared with patients with early or without AFOP and specifically associated with development of restrictive allograft syndrome (OR 28.57, 95% CI 11.34-67.88; p<0.0001). Similarly, graft survival was significantly lower in patients with late AFOP (median survival 4.39 years; p<0.0001) compared with patients with early AFOP or without AFOP. Late AFOP was furthermore associated with detection of circulating donor-specific antibodies (OR 4.75, 95% CI 2.17-10.60; p=0.0004) compared with patients with early or without AFOP, and elevated airway and blood eosinophilia (p=0.043 and p=0.045, respectively) compared with early AFOP patients.Late new-onset AFOP is associated with a worse prognosis and high risk of CLAD development, specifically restrictive allograft syndrome. Our findings indicate that late new-onset AFOP might play a role in the early pathogenesis of restrictive allograft syndrome.

Asthma progression and mortality: the role of inhaled corticosteroids.

Overall, asthma mortality rates have declined dramatically in the last 30 years, due to improved diagnosis and to better treatment, particularly in the 1990s following the more widespread use of inhaled corticosteroids (ICSs). The impact of ICS on other long-term outcomes, such as lung function decline, is less certain, in part because the factors associated with these outcomes are incompletely understood. The purpose of this review is to evaluate the effect of pharmacological interventions, particularly ICS, on asthma progression and mortality. Furthermore, we review the potential mechanisms of action of pharmacotherapy on asthma progression and mortality, the effects of ICS on long-term changes in lung function, and the role of ICS in various asthma phenotypes.Overall, there is compelling evidence of the value of ICS in improving asthma control, as measured by improved symptoms, pulmonary function and reduced exacerbations. There is, however, less convincing evidence that ICS prevents the decline in pulmonary function that occurs in some, although not all, patients with asthma. Severe exacerbations are associated with a more rapid decline in pulmonary function, and by reducing the risk of severe exacerbations, it is likely that ICS will, at least partially, prevent this decline. Studies using administrative databases also support an important role for ICS in reducing asthma mortality, but the fact that asthma mortality is, fortunately, an uncommon event makes it highly improbable that this will be demonstrated in prospective trials.

The persistence of allergen exposure favors pulmonary function decline in workers with allergic occupational asthma

In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation. This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers. Two groups of workers with allergic OA were selected. The first group (30 workers) changed job after the diagnosis and was no more exposed to sensitizing allergens, and the second group (28 subjects) did not and, as a consequence of preventive measures in the work place, was exposed to a lower level of allergens. All were treated with conventional therapy, according to GINA protocols. FEV1 changes during a 12-year period were evaluated. Despite pharmacological therapy, the pulmonary function decay slope was steeper in workers continuously exposed to the sensitizing agent (even at reduced level) than in those with a complete cessation of exposure: final FEV1 loss was 512.5 ± 180 ml versus 332.5 ± 108 ml, respectively. The difference became significant after 4 years from the cessation of the exposure. The study shows that the cessation of the exposure to allergen in the work place appears the most effective measure in limiting pulmonary function decline in asthmatic workers and underlines the importance of allergic risk assessment and control in the management of occupational asthma.

Complex two-gene modulation of lung disease severity in children with cystic fibrosis

Although cystic fibrosis (CF) is a monogenic disease, its clinical manifestations are influenced in a complex manner. Severity of lung disease, the main cause of mortality among CF patients, is likely modulated by several genes. The mannose-binding lectin 2 (MBL2) gene encodes an innate immune response protein and has been implicated as a pulmonary modifier in CF. However, reports have been conflicting, and interactions with other modifiers have not been investigated. We therefore evaluated the association of MBL2 with CF pulmonary phenotype in a cohort of 1,019 Canadian pediatric CF patients. MBL2 genotypes were combined into low-, intermediate-, and high-expression groups based on MBL2 levels in plasma. Analysis of age at first infection with Pseudomonas aeruginosa demonstrated that MBL2 deficiency was significantly associated with earlier onset of infection. This MBL2 effect was amplified in patients with high-producing genotypes of transforming growth factor beta 1 (TGFB1). Similarly, MBL2 deficiency was associated with more rapid decline of pulmonary function, most significantly in those carrying the high-producing TGFB1 genotype. These findings provide evidence of gene-gene interaction in the pathogenesis of CF lung disease, whereby high TGF-beta1 production enhances the modulatory effect of MBL2 on the age of first bacterial infection and the rate of decline of pulmonary function.

Does harboring hostility hurt? Associations between hostility and pulmonary function in the Coronary Artery Risk Development in (Young) Adults (CARDIA) study.

To examine the cross-sectional association between hostility and pulmonary function (PF) and its consistency across race/ethnicity-gender groups. Data were from the Coronary Artery Risk Development in (Young) Adults (CARDIA) cohort study (N=4,629). Participants were recruited from 4 metropolitan areas in the United States, ages 18-30 years at baseline in 1985-1986, approximately balanced across race/ethnicity (Black, White) and gender. Main outcome measures were percent predicted values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). In full-sample multiple linear regression analyses, each 1 standard deviation (SD) increase in hostility was associated with a 0.66% decrease in FEV-sub-1 (p=.0002) and a 0.60% decrease in FVC (p=.0006). This inverse association of hostility with PF remained after controlling for age, height, current socioeconomic status (SES), participant smoking status, and asthma and is more consistent than that of smoking and PF. In stratified analyses, each 1 SD increase in hostility predicted statistically significant reductions in PF for Black women, White women, and Black men. For White men, hostility showed no statistically significant relation with PF, although the pattern relating hostility to PF was similar to the pattern in the other three groups. Further, both of the post hoc three-way interaction terms for hostility, race/ethnicity, and gender predicting FEV-sub-1 and FVC were nonsignificant. PF was inversely associated with hostility across race/ethnicity and gender, independent of age, height, current SES, smoking, and asthma. On the basis of these cross-sectional findings, the authors hypothesize that higher hostility will predict a more rapid decline in PF.

Thirty-Year Cumulative Incidence of Chronic Bronchitis and COPD in Relation to 30-Year Pulmonary Function and 40-Year Mortality: A Follow-up in Middle-Aged Rural Men

To describe the 30-year cumulative incidence of chronic bronchitis and COPD in relation to smoking habits. The effect of chronic bronchitis on pulmonary function and mortality was also examined. Middle-aged men belonging to two rural Finnish cohorts of the Seven Countries Study (n = 1,711 in 1959) were followed up for up to 40 years until 2000. Standard questionnaires were used to measure chronic bronchitis, and repeated spirometry was used to evaluate pulmonary function during the 30 years. Forty-year mortality data were examined. The cumulative incidence of chronic bronchitis and COPD was 42% and 32%, respectively, in continuous smokers, compared to 26% and 14% in ex-smokers and 22% and 12% in never-smokers. During the follow-up, subjects with chronic bronchitis had on average 252 mL (95% confidence interval, 211 to 293 mL) lower forced expiratory volume than those without it. The decrease in forced expiratory volume attributable to chronic bronchitis was most pronounced in those with persistent symptoms and in smokers. In subjects with chronic bronchitis, all-cause mortality was increased by a hazard ratio of 1.30 (95% confidence interval, 1.02 to 1.65). Smokers with chronic bronchitis who decreased their daily cigarette consumption increased their median life span by 2.4 years. The lifetime risk of chronic bronchitis among smokers is approximately two in five, and almost one half of smokers who have chronic bronchitis also acquire COPD. Chronic bronchitis is related to earlier death, also in never-smokers, probably partly through a rapid decline in pulmonary function.

Airflow limitation and changes in pulmonary function among bleachery workers

This study investigated whether chronic airflow limitation and rapid decline in pulmonary function were associated with peak exposures to ozone and other irritant gases in pulp mills. Bleachery workers potentially exposed to irritant gassings (n = 178) from three Swedish pulp mills, and a comparison group of workers not exposed to irritant gassings (n = 54) from two paper mills, were studied. Baseline surveys occurred in 1995-1996, with follow-up surveys in 1998-1999. Participants performed spirometry and answered questions regarding ozone, chlorine dioxide (ClO2), and sulphur dioxide (SO2) gassings. From regression models controlling for potential confounders, declines in both the forced expiratory volume in one second (FEV1) (-24 mL x yr(-1)) and the forced vital capacity (FVC) (-19 mL x yr(-1)) were associated with ClO2/SO2 gassings. At follow-up, the prevalence of chronic airflow limitation (i.e. FEV1/FVC less than the lower limit of normal) was elevated for participants with only pre-baseline ozone gassings and with both pre-baseline and interval ozone gassings, after controlling for potential confounders. These findings suggest that obstructive effects among bleachery workers are associated with ozone gassings, and that adverse effects on spirometry might also accompany chlorine dioxide/sulphur dioxide gassings. Peak exposures to irritant gases in pulp mills should be prevented.

Impact of cystic fibrosis-related diabetes (CFRD) on lung transplant outcomes

The National Cystic Fibrosis Registry reveals that CFRD is associated with decreased survival and a more rapid decline in pulmonary function. We hypothesized that CFRD could produce similar effects after lung transplantation (LTX). Data from our center reveals that by 1 year post-LTX, CFRD patients have an increased incidence of infections (INF)(15/18 vs 5/15, p<.05 Fisher’s Exact Test), an earlier onset of bronchiolitis obliterans syndrome (BOS) (5/15 vs 0/15, p<.05) and a trend towards increased acute rejection (REJ) compared to non-CFRD patients. To validate our results suggesting CFRD adversely affects LTX outcomes, we analyzed the UNOS database.

Longitudinal analysis of pulmonary function decline in patients with cystic fibrosis

Background: Chronic progressive lung disease is the most prominent cause of morbidity and death in patients with cystic fibrosis (CF), but severity of lung disease and rate of lung function decline are widely variable. Accurate estimates of decline have been difficult to define and compare because the timing of measurements and duration of follow-up differ in various patient groups. Patients: Three hundred sixty-six patients with CF, born from 1960 to 1974, were selected from a CF database birth cohort if they had two or more measurements of pulmonary function, at least one of which was performed before the age of 10 years. Methods: Mixed model regression analysis provided estimates of the average rate of decline of spirometry measurements in subgroups on the basis of survival age, sex, pancreatic status, and genotype. Results: Patients who died before the age of 15 years had significantly poorer pulmonary function when first tested and a more rapid decline in pulmonary function thereafter than patients who survived beyond the age of 15 years. In the latter, functional levels at the age of 5 years were normal, but average rates of decline were significantly related to survival age. Female patients had significantly steeper decline than male patients, and those with pancreatic insufficiency had much steeper decline than those with pancreatic sufficiency. In the subset of 197 who survived to 1990 and were subsequently genotyped, rate of decline was greater in those homozygous for the ΔF508 mutation, compared with those who were heterozygous for ΔF508 or those who had two other mutations. Discussion: All but the most severely affected patients, who died before age 15, appear to have had normal pulmonary function when first tested in early childhood. Pancreatic sufficiency, male gender, and some non-ΔF508 mutations are associated with a slower rate of pulmonary function decline. Mixed model analysis is a valuable tool for describing and comparing pulmonary function decline in groups of patients with CF. (J Pediatr 1997;131:809-14)

Colchicine Versus Prednisone as Treatment of Usual Interstitial Pneumonia

To assess the results with colchicine and prednisone as initial single-drug therapy in patients with usual interstitial pneumonia (UIP). We reviewed the serial pulmonary function test results in 22 patients with typical clinical and high-resolution computed tomographic features of UIP who were treated with colchicine as initial single-agent therapy and compared them with a group of 22 historical patients with UIP of similar severity diagnosed by open-lung biopsy who were given prednisone as initial single-drug therapy. No significant difference was detected in the rate of decline of pulmonary function or in the time to "failure" between the two study groups. A trend was suggested for more rapid decline of pulmonary function in the prednisone-treated than in the colchicine-treated group. The design of this study does not allow distinction between a possible beneficial effect of colchicine and a possible adverse effect related to weaning from high-dose prednisone. Colchicine was well tolerated; few side effects other than mild diarrhea were noted in those patients able to take the drug long enough to return for pulmonary function testing at 3 months. In comparison, the side effects of prednisone were more serious and were not always reversible with cessation of therapy. This study lends further support to the assumption that colchicine may be a satisfactory and less hazardous substitute for prednisone in the treatment of patients with UIP.

SLOWING THE DETERIORATION OF ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE OBSERVED DURING BRONCHODILATOR THERAPY BY ADDING INHALED CORTICOSTEROIDS: A 4-YEAR PROSPECTIVE STUDY

Purpose of the Study. To determine if the deterioration in lung function, seen in adults with asthma or chronic obstructive pulmonary disease (COPD), could be reversed or slowed by the addition of inhaled beclomethasone. Many short-term studies have shown the benefits of inhaled steroids in asthma; in particular, their ability to improve pulmonary function, decrease bronchial hyperreactivity, and reduce symptoms. Few studies have evaluated the long-term effects of inhaled steroids on the clinical course of either asthma or COPD. Methods. This report is an extension of a 2-year study that followed 160 patients with asthma or COPD on bronchodilator therapy alone. From this group, 56 patients who displayed a rapid decline in pulmonary function (FEV1 ≥ 80 ml/year) and a high exacerbation rate (≥1/year) were selected to receive additional treatment with beclomethasone dipropionate 400 µg two times daily over 4 years. FEV1 and airways responsiveness to histamine were measured every 6 months and at 1 and 13 months upon completion of the study. Peak flows and symptom scores were recorded weekly, and compliance, inhaler technique, and adverse affects were monitored every 3 months. Findings. During the first 6 months of beclomethasone treatment, both groups showed a significant improvement in pre- and postbronchodilator FEV1 with the most significant change noted in the asthma group. Thereafter, the FEV1 began to decline again, as it had in the first 2 years of the study, but at a rate that was 33% slower. In addition to slowing the decline in FEV1, inhaled beclomethasone resulted in a substantial decrease in the degree of bronchial hyperreactivity, and peak flow rates improved.

The role of allergy and nonspecific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease.

Although the information that has been reviewed leaves many questions unanswered, some conclusions can be drawn from available data. (1) Smoking appears to increase the risk of sensitization to certain inhaled antigens encountered in the workplace; however, there is no definite evidence that smoking increases the frequency or intensity of allergy to common aeroallergens in the general population. On average, smokers have higher serum total IgE concentrations and blood eosinophil counts than do nonsmokers, but the mechanisms underlying these alterations are not clear. Analysis of these relationships is complicated by observations suggesting that atopic persons are less likely to become and to remain regular cigarette smokers. (2) Long-term cigarette smoking may be associated with increased nonspecific airway responsiveness, although the magnitude of this effect is relatively small when one adjusts for prechallenge level of pulmonary function. This effect of smoking may be more pronounced in atopic persons. (3) Atopy, as assessed by skin testing and serum IgE concentrations, is associated with asthma, nonspecific airway hyperresponsiveness, and reduced pulmonary function level in population data. However, there is no clear evidence that atopy is a risk factor for irreversible airflow obstruction in persons without asthma. Population data do not indicate how much of the reduction in pulmonary function associated with atopy and asthma is potentially reversible. (4) Blood eosinophil count appears inversely related to the level of pulmonary function and directly related to the rate of decline of pulmonary function among nonsmokers. Reports vary concerning whether the relationship of eosinophil count to level of pulmonary function remains after excluding subjects with diagnosed asthma. This relationship may be determined largely by a clinically distinguishable subset of nonsmokers with "asthmatic bronchitis." Presumably, these observations reflect an adverse impact of eosinophilic inflammation in the airways or lung parenchyma. It is not clear whether this represents an allergic response because skin-test reactivity to common aeroallergens and serum total IgE concentration do not show similar relationships to reduced level and rapid decline of pulmonary function. (5) Among smokers, nonspecific airway hyperresponsiveness appears to be associated with an accelerated longitudinal decline of pulmonary function, although most studies indicating this association are limited by either a retrospective design or lack of adjustment for prechallenge level of pulmonary function.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulmonary Function in Obligate Heterozygotes for Cystic Fibrosis

Airway reactivity is associated with rapid decline in pulmonary function with age or packyears of smoking in otherwise normal subjects. Because heterozygotes for cystic fibrosis (CFHZ) have a higher prevalence of airway reactivity than do controls, we tested the hypothesis that CFHZ have a more rapid decline in pulmonary function with age or packyears of smoking than do controls. We performed spirometry on 280 parents of children with CF and 280 age-matched control parents of children with heart disease. The ALA-DLD-78 questionnaire was also administered to these volunteers. Although the CF parents report wheezing apart from a cold more frequently than control parents, they show no greater decline of pulmonary function (FEV1, FEF25-75%, or FEV1/ht3) with age or packyears of smoking than do controls. The complaint of wheezing apart from a cold contributes significantly to the variance of FEV1 and FEF25-75% even when the effects of height, age, packyears of smoking, sex, and CF heterozygosity are controlled. The hypothesis that obligate heterozygotes for CF have increased age- or smoking-related decline in airflow is not supported by these data. Instead, the results suggest that any pulmonary function abnormalities associated with CF heterozygosity are small and not clinically significant and that CF heterozygosity per se is not a major risk factor for development and progression of obstructive airways disease.

Effects of ozone on lung and somatic growth. Pair fed rats after ozone exposure and recovery periods

Minor differences in lung growth and development during childhood have been considered as a potential cause of rapid decline in pulmonary function in adulthood. Inhalation of ozone commonly causes changes in both body weight and lung volumes, which complicates interpretation of any changes in lung growth. The effects of ozone on lung growth were studied in rats which were pair fed. This technique permitted comparison of ozone-exposed and filtered-air control rats of the same body weight and body size as well as age and sex. Exposure was to filtered air or to 0.64 or 0.96 ppm ozone (UV standard) 8 h/night for 42 nights. A second control group was fed ad libitum and exposed to only filtered air. Half the rats were studied at the end of the 42-night exposures, the rest after a 42-day post-exposure period during which all rats were fed ad libitum and breathed filtered air. Rats examined at the end of the exposure period had larger saline and fixed lung volumes. These larger lungs had greater volumes of parenchyma, alveoli and respiratory bronchioles. Some of these changes persisted throughout a 42-day post-exposure period. Ozone inhalation by young rats alters lung growth and development in ways likely to be detrimental and those changes persist after ozone inhalation stops.