Effect of weight gain on pulmonary function after smoking cessation in the Lung Health Study.

The objective of this study was to determine if the weight gain that accompanies smoking cessation is independently associated with reductions in FEV1 and FVC, using a multicenter randomized intervention trial of smoking cessation in 10 communities in the United States and Canada. Enrollees were currently smoking women and men 35 to 60 yr of age with mild-to-moderate airway obstruction. Participants were randomized to one of three study groups: an intensive smoking cessation program with an inhaled bronchodilator (or a placebo), and usual care. Changes in absolute and percent predicted FEV1 and FVC between baseline and fifth annual follow-up visit were monitored in relation to changes in body weight during the interval. At the baseline examination, percent predicted FEV1 was maximal at 90 to 100% ideal body weight (IBW) and was lower as body weight deviated from this range. The FVC decreased linearly when IBW exceeded 100%. Weight gain was greatest during the first 12 mo after smoking cessation. Weight gain was associated with lower fifth-year FEV1 and FVC in all smoking categories: continuous smokers, intermittent smokers, and sustained quitters. The FVC was affected by weight gain more than was the FEV1, and the FEV1 was affected by smoking cessation more than FVC. Men showed more impairment of FVC with weight gain than did women, possibly because of differential patterns of fat deposition. In sustained quitters, after adjustment for baseline factors, the estimated reduction of FVC was 17.4 ml/kg weight gain for men and 10.6 ml/kg for women. The estimated loss of FEV1 was 11.1 ml/kg weight gain for men and 5.6 ml/kg for women. Lung function after smoking cessation is significantly influenced by weight gain and affects men more than women. The deleterious effects of weight gain are small, however, in comparison with the beneficial effects of smoking cessation.

Severe restrictive lung disease in systemic sclerosis.

OBJECTIVE: We sought to identify risk factors for developing severe restrictive lung disease and to determine the time of onset and rate of progression in patients with systemic sclerosis (SSc). METHODS: Using the University of Pittsburgh Scleroderma Databank, we grouped patients according to their lowest forced vital capacity (FVC) value: > 75% predicted, 50-75% predicted, and < 50% predicted. In patients with severe restrictive disease, we examined serial pulmonary function test (PFT) results to determine the rate of loss of lung volume over time. RESULTS: Of 890 SSc patients, 60% (n = 531) never had an FVC < or = 75% predicted; 27% (n = 243) had moderate restrictive disease, with an FVC value of 50-75% predicted; and only 13% (n = 116) of the patients had severe restrictive disease, with FVC < or = 50% predicted. Black race, male sex, early disease, and primary cardiac involvement due to SSc were the features most frequently associated with severe restrictive lung disease (by multiple logistic regression). Fifty-five patients with severe restrictive lung disease had their first of at least 2 PFTs during the first 5 years after onset of any SSc (not pulmonary) symptoms. In 30 patients, the FVC declined by 32% per year in the first 2 years of illness, in 16 patients the annual loss was 12% in years 2-4 after disease onset, and in 9 patients annual loss was 3% during years 4-6 of disease (P < 0.005 by 1-way analysis of variance). CONCLUSION: In SSc patients, black men with early disease who have cardiac involvement are the most likely to have factors associated with the development of severe restrictive lung disease (which is increasingly becoming a major cause of death). Disease subtype (diffuse versus limited cutaneous) and serum anti-topoisomerase I antibody do not differentiate between moderate and severe restrictive disease. Careful monitoring of pulmonary function early in the disease, when the greatest loss of lung function occurs, may help identify patients likely to respond to new therapy.

Therapy for severe interstitial lung disease in systemic sclerosis. A retrospective study.

OBJECTIVE: This retrospective observational study attempted to determine whether any of the therapies used in the management of systemic sclerosis (SSc) patients held potential benefit for patients with interstitial lung disease. METHODS: All patients with SSc who had a pulmonary function test (PFT) showing a forced vital capacity (FVC) of < 70% predicted and an additional PFT at least 4 months later were grouped according to the treatment they received. Changes in pulmonary function were analyzed by the mean percent predicted FVC from the initial and the final test, and by the rate of percent change in FVC (ml/year) in the first 2 years after therapy. Bronchoalveolar lavage was performed in a subset of these patients. RESULTS: Of 363 SSc patients who had an FVC < 70% predicted, 122 had a second PFT and fulfilled the criteria for one of the following drug groups: high-dose prednisone (n = 21), immunosuppressive other than cyclophosphamide (CYC) (n = 16), CYC (n = 14), D-penicillamine (n = 37), or no drug (n = 34). In both analyses, the CYC-treated group showed significantly more improvement in FVC than did the other groups. Patients with early disease had the greatest likelihood of responding to any drug. CONCLUSION: This retrospective study shows that patients treated with CYC had a significant improvement in FVC over time. Prospective controlled studies of CYC treatment in early disease are necessary to determine if it can significantly alter the natural history of interstitial lung disease.

Chronic Obstructive Pulmonary Disease Early Intervention Trial (Lung Health Study). Baseline characteristics of randomized participants.

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The hypothesis being tested is that over a 5-year period, a comprehensive intervention program can reduce both the rate of decline in pulmonary function and the rates of respiratory morbidity and mortality in middle-aged smokers with mild to moderate airflow obstruction. The primary outcome variable of the trial is the annual rate of decline of maximum postbronchodilator FEV1. Secondary outcomes are the development of respiratory and nonrespiratory morbidity and mortality. After screening 73,694 cigarette smokers, aged 35 to 60 years, 5,887 participants were randomized into three equal groups: usual care, smoking intervention with daily use of a metered-dose inhaler with ipratropium bromide, and smoking intervention with inhalation of placebo. Eligible participants had a ratio of FEV1 to forced vital capacity (FVC) of 70 percent or less, were free of known life-limiting conditions, expressed willingness to enter the intervention program if so randomized, and gave written informed consent prior to entry into the trial. Spirometry, methacholine challenge, and questionnaires were strictly standardized within and across centers. The purpose of this report is to describe the characteristics of randomized participants at the time of entry into the study. For both sexes, three measures of lung function--average cross-sectional FEV1/FVC ratio, FEV1, and FEV1 percentage of predicted normal--showed slight downward trends for each successively older 5-year age cohort. The increase in FEV1 after isoproterenol was 15 percent or more in only 2.4 percent of men and 2.8 percent of women. A positive response to methacholine (defined as a fall in FEV1 of > 20 percent from baseline at concentrations up to 25 mg/ml) occurred in 63 percent of men and 87 percent of women. The cross-sectional prevalences of cough, phlegm, wheeze on most days or nights, and shortness of breath were 49 percent, 43 percent, 32 percent, and 43 percent, respectively. Respiratory symptoms were reported by a higher proportion of participants in the younger age groups than in the older age groups. Participants who reported cough, phlegm, and/or wheeze averaged lower FEV1 percent predicted and higher probability of positive response to methacholine than participants who did not. Shortness of breath appeared to be significantly associated with lower lung function and higher reactivity in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

A solid-phase assay for the detection of anti-sperm antibodies.

PROBLEM: ELISA is an ideal assay method for a large-scale screening of anti-sperm antibodies among a large number of infertile males. However, conventional ELISA with whole spermatozoa needs time-consuming steps of centrifugation. METHOD: A solid-phase assay used for detecting anti-sperm antibodies was established. This assay is suitable not only for detecting circulating anti-sperm antibodies of IgG, IgM, and IgA subclass simultaneously but also for screening hybridomas secreting anti-sperm monoclonal antibodies (mAbs). The microtiter plates, on which solubilized sperm antigens are fixed, can be stored at -80 degrees C for up to six months without losing reactivity with anti-sperm antibodies. RESULTS: Using this assay, 53 sera (13 were proven positive and 40 were proven negative for sperm agglutination antibody) were tested. Although the false-negative rate was 0%, the false-positive rate was 32%. One thousand one hundred sixty-five supernatants from hybridomas constructed with splenocytes of mice who were hyperimmunized with human sperm and nonsecreting myeloma cells were tested by this solid-phase assay and two anti-sperm mAb secreting clones were selected and established. CONCLUSIONS: It is recommended that for research work this assay could be used for the first screening of the hybridoma secreting anti-sperm mAb, and for clinical use this assay might be suitable for the first screening of sera of infertile patients. However, conventional bioassays should follow to confirm the biological meaning of the positivity.

Recruitment of participants in the Lung Health Study, I: Description of methods.

The recruitment experience is described for a large multicenter clinical trial, the Lung Health Study, which required the screening of more than 73,000 male and female smokers aged 35-60. This paper summarizes the plans, methods, and recruiting experience of the 10 participating clinical centers. Recruitment proposals were prepared by each clinical center as part of the contract application process. Recruitment directors and staff were appointed whose primary responsibility was recruitment. Only one clinical center retained its original plan throughout; most clinical centers achieved their recruitment goals by supplementing their originally proposed strategies with one or more methods. The most frequently used methods were worksite, public site, mass mail, telephone, media, and referral strategies. The most significant contributions to the success of the recruitment process were the willingness and initiative of the clinical centers' staff to explore alternative techniques that would take advantage of local circumstances and their ability to incorporate as many workable recruitment methods as necessary to achieve the goal.

Public screening for lung disease: experience with the NIH Lung Health Study.

The Lung Health Study is the first major initiative of the National Heart, Lung, and Blood Institute in screening for and intervention in early lung disease. The objective of the study is to identify cigarette smokers who have early disease and determine whether an intervention program of smoking cessation and bronchodilator therapy will alter the course of their disease. After an extensive screening program, 5,887 participants have been randomized to one of three groups: usual care, intervention with smoking cessation and the use of a placebo inhaler, and intervention with smoking cessation and the use of ipratropium bromide. All participants will be followed for 5 years. Preliminary data from the screening indicate that chronic obstructive pulmonary disease is more prevalent than was previously recognized, that it is widespread in women as well as men, and that it is far more common in young individuals than was thought. Approximately two-thirds of the study participants have hyperreactive airways. Preliminary data from the Lung Health Study indicate that screening for lung function can be carried out in a cost-effective manner.

The effect of obliterative bronchiolitis on breathing pattern during exercise in recipients of heart-lung transplants.

The more rapid and shallow ventilation pattern seen during exercise in patients with obstructive and/or restrictive lung disease has been attributed by some investigators to the effects of vagal afferents from intrapulmonary receptors. Recipients of heart-lung transplants (HLTR) offer a unique opportunity to test this hypothesis since they have denervated lungs and may develop obliterative bronchiolitis after organ rejection. We thus compared the ventilation responses to incremental bicycle ergometry of five HLTR with relatively normal pulmonary function (HLTR-N) and four with bronchiolitis obliterans (HLTR-O). We compared the slopes of the linear portion of the tidal volume versus inspired minute ventilation relationship of both groups. The rate of rise of tidal volume (VT) (slope of VT versus VI) was greater in HLTR-N (0.31 +/- 0.004) than in HLTR-O (0.023 +/- 0.007) (p less than 0.05). This corresponded to a slower increase in respiratory rate (RR) (slope of RR versus Vl/cm) in HLTR-N (0.055 +/- 0.005) than in HLTR-O (0.083 +/- 0.019) (p less than 0.01). Furthermore, values for VT, inspiratory time (TI), and duty cycle (TI/Ttot) measured during exercise at the VT break point were all significantly lower in the HLTR-O than in HLTR-N. We also evaluated the ability of HLTR with lung disease to regulate their ultimate level of ventilation during maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

The short-term effects of smoke exposure on the pulmonary function of firefighters.

The short-term effects of smoke inhalation have been little studied. This study evaluated whether firefighters experience a significant change in spirometric values following exposure to smoke from a fire. Sixty firefighters from the city of Pittsburgh completed a questionnaire (Medical Research Council) and underwent spirometric testing following exposure to house fires. The group contained 25 current smokers, 14 ever smokers, and 21 never smokers. Firefighters reporting cough, phlegm, breathlessness, and chest illnesses were more likely to be current or ever smokers than never smokers. Mean spirometric data obtained before exposure, after a minimum of four off-duty days, showed the following: FVC, 4.50 +/- 0.60L (90 percent of predicted); FEV1, 3.65 +/- 0.56L (96 percent of predicted); FEV1/FVC, 81 +/- 8 percent (106 percent of predicted); FEF25-75%, 3.71 +/- 1.13L/s (96 percent of predicted); and PEF, 7.95 +/- 1.70L/s (87 percent of predicted). After exposure, spirometry was performed on 22 firefighters. All spirometric values decreased after exposure; however, a significant decline was only seen in two indices, the FEV1 and FEF25-75%. This decline was small (3 to 11 percent). Two firefighters experienced an exaggerated decline in spirometric values after exposure, compared to the group as a whole. Neither age, smoking history, location of firefighting, intensity of smoke exposure, or use of a self-contained breathing apparatus explained the reasons for the greater decline in these two individuals. Thus, while firefighters do experience a small decrease in pulmonary function after exposure to house fires, there appears to be a small subgroup of firefighters who develop more substantial and potentially clinically important decreases in pulmonary function after smoke exposure.

Giant-cell interstitial pneumonia and hard-metal pneumoconiosis. A clinicopathologic study of four cases and review of the literature.

We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provoke an investigation of occupational exposure.

Ventilation and breathing pattern during progressive hypercapnia and hypoxia after human heart-lung transplantation.

The effects of human pulmonary denervation on the ventilatory responses to progressive hyperoxic hypercapnia and isocapnic hypoxia as well as the effect on resting breathing pattern were evaluated in nine female heart-lung transplant (H-LT) recipients. The results were compared to those obtained from 10 normal women of comparable age and stature. Testing was performed 2 to 37 months after H-LT (median, 7.5 months). Cardiac function was normal in all H-LT recipients. None of the patients had spirometric evidence of airway obstruction, while six had a restrictive pattern with forced vital capacities less than 80% of predicted values. Resting minute ventilation (VE), tidal volume (VT), and ventilatory drive (VT/TI) in the H-LT recipients were not significantly different from those of the normal subjects. Inspiratory time (TI), however, was significantly shorter in the H-LT patients (1.64 +/- 0.2 versus 2.09 +/- 0.13 s, p = 0.035), and resting breathing frequency (F) tended to be greater in the H-LT recipients (16.27 +/- 2.04 versus 12.82 +/- 0.53 breaths/min, p = 0.052). The overall ventilatory response to hypercapnia was reduced after H-LT (0.91 +/- 0.17 versus 1.5 +/- 0.27 L/min/mm Hg CO2, p less than 0.043), as was the F response (0.2 +/- 0.09 versus 0.65 +/- 0.13 breaths/min/mm Hg CO2, p less than 0.01). The VT and VT/TI responses to hypercapnia did not differ between the H-LT recipients and normal subjects. There were no significant differences between the two groups with respect to the responses to progressive hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Breathing during wakefulness and sleep after human heart-lung transplantation.

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence of an altered pattern of breathing during exercise in recipients of heart-lung transplants.

Recipients of heart-lung transplants represent an unusual opportunity to study the regulation of ventilation, because the neural pathways between the lungs and the central nervous system are disrupted in these patients. We compared the ventilation response in seven recipients of heart-lung transplants who had normal pulmonary function and seven recipients of heart transplants, all of whom performed incremental bicycle ergometry. The level of ventilation in recipients of heart-lung transplants was similar to that in heart-transplant recipients for equivalent levels of carbon dioxide production. Arterial pH and partial pressure of carbon dioxide at maximal exercise were normal and not significantly different in the two groups, also suggesting that levels of ventilation were appropriate in both groups. However, the rate of the rise in respiratory rate for increasing levels of ventilation was significantly lower in recipients of heart-lung transplants than in heart-transplant recipients, and the initial increase in tidal volume was more rapid in the former group than in the latter. Thus, recipients of heart-lung transplants have an appropriate level of ventilation during exercise as the result of a disproportionate increase in tidal volume at a reduced respiratory rate. We speculate that intrapulmonary receptors are important in regulating the pattern, but not the absolute level, of ventilation during exercise.

Comparison of arm and leg ergometry in patients with moderate chronic obstructive lung disease.

Exercise testing is traditionally performed with leg exercise on either a treadmill or a bicycle ergometer. Many of these tests are terminated before dyspnoea occurs because of leg fatigue, arthritic pain, or claudication. A study was carried out to determine whether arm ergometry testing might serve as an alternative method to leg testing in eight patients with chronic obstructive lung disease. The patients had mild to moderate dyspnoea on exertion and required bronchodilator treatment. They had smoked an average of 62 pack years and had a mean FEV1 of 1.88 l. Arm and leg ergometry yielded similar levels of maximum ventilation (arm 47.2, leg 48.6 l/min), maximum heart rates (126 v 124 beats/min), maximum tidal volume (1.5 v 1.6 l), and respiratory rate (30 v 29 breaths/min); but maximum oxygen consumption (1120 v 966 ml/min), maximum power output (62 v 26 w), and oxygen pulse (9.1 v 7.8 ml/beat) were all higher with leg than with arm ergometry. In addition, ventilation and heart rate at a given level of oxygen consumption were higher for arm than for leg work during both submaximal and maximal exercise. It is concluded that arm ergometry offers an alternative testing method to leg testing in patients with moderate chronic obstructive lung disease.

Asbestosis among electricians.

In a cross-sectional study of a small group of non-shipyard electricians, the prevalence of asbestosis, defined as irregular opacities of at least 1/0 profusion, was found to be 15% overall and 25% after 20 years of service. Irregular opacities occurred more frequently among smokers. Cost estimates for asbestos-related disease should include construction electricians in the populations at risk.