RATIONALE: Patients hospitalized for severe asthma exacerbations are at increased risk of re-exacerbations after discharge home (DC). We hypothesized that persistent airflow obstruction 2 wks after DC predicts increased risk of asthma re-exacerbation. METHODS: Adults (≥18 yrs) hospitalized with physician diagnosis of asthma exacerbation without other chronic respiratory disorders were eligible. Spirometry was obtained at DC and 2 wks after DC. Adherence to corticosteroid therapy after DC (prednisone 40 mg/d X 7d with fluticasone MDI 880 ug/d) was electronically monitored. Medical records at 12 hospitals were reviewed to identify re-exacerbations (ED visits or hospitalization for asthma) within 90d of DC. RESULTS: 38 participants were enrolled (age 44.5 yrs (10.5) [mean (SD)], 73.7% female, 92.1% African-American, duration of asthma 27 yrs (15)). At DC, FVC=64.2% (15.6%), FEV1=51.7% (16.2%), and FEV1/FVC=79.8% (13.9%) predicted. The mean (range) % change in airflow obstruction after DC was: FVC 28.8% (−12.4 to 83.3%), FEV1 39.4% (−22.2 to 185.6%), and FEV1/FVC 7.1% (−20.5 to 66.7%). Adherence to prednisone and fluticasone was 63% and 58% prescribed, respectively. Eight subjects (21%) had an asthma re-exacerbation. In a multivariable model, the only independent predictor of asthma re-exacerbation was a lower FEV1/FVC % predicted at 2 wks (relative risk for 10-unit change = 1.78 [95% CI 1.06-2.94]). Lung function at DC and adherence to corticosteroid therapy were not associated with asthma re-exacerbation. CONCLUSIONS: Lower FEV1/FVC 2 wks after DC was associated with greater risk of asthma re-exacerbation. A lower FEV1/FVC is an early predictor of asthma re-exacerbation.

The title of this paper is intentionally provocative, but an accurate characterization of what this paper is about: a theory of the mechanism of the airway hyperresponsiveness (AHR) in asthma. In non-insulin-dependent diabetes mellitus (type II diabetes), there is compelling evidence that the fundamental cause of the glucose intolerance results from decreased sensitivity to insulin [1]. The theory presented in this paper is that the fundamental cause of the AHR in asthma results from a decreased sensitivity to endogenous nitric oxide (NO).

This study was performed to determine the degree to which beta2-adrenergic receptor agonists can reverse the allergen-induced late reduction in lung function. On two occasions, seven asthmatic subjects were administered terbutaline or its vehicle by intravenous infusion 7 h after inhaled allergen, at which point the forced expiratory volume in 1 s was 57% of baseline. On another occasion, terbutaline was infused at baseline to determine maximal attainable bronchodilation. After allergen challenge, terbutaline rapidly improved lung function. At the end of terbutaline infusion, the forced expiratory volume in 1 s reached 100 +/- 1.3% of baseline and 84.2 +/- 4.3% of maximal attainable value, but the bronchodilating effect of the beta-agonist did not plateau. The values for forced vital capacity were 102 +/- 1.3% of baseline and 95.1 +/- 3% of maximal attainable value. The kinetics of the terbutaline effect, when it was infused at baseline, were similar to those in the late phase. Because the late-phase reduction in lung function is rapidly reversible by beta2-adrenergic agonists, we conclude that it is caused mainly by bronchial smooth muscle spasm.

The isolated, autologous blood perfused canine lung develops spontaneous edema which is largely dependent on the presence of oxygen (O/sub 2/). Whether this O/sub 2/-effect was mediated by the formation of toxic O/sub 2/ products or by another nonspecific effect of O/sub 2/ was unknown. To distinguish between these possibilities, the effect of catalase (CAT), a scavenger of hydrogen peroxide (H/sub 2/O/sub 2/), was examined in this model. Lung weight gain was recorded over a 5 hour perfusion period during ventilation with (1) F/sub I/O/sub 2/ .95; (2) F/sub I/O/sub 2/ 0; (3) F/sub I/O/sub 2/ .95 + CAT 100 ..mu..g/ml added to the perfusate. (n = 18, F/sub I/CO/sub 2/ .05). Perfusion rate (Q) was titrated to a mean arterial pressure (Ppa) of 15 mmHg at 30 min and held constant thereafter. At similar Q (260 +/- 37 ml/min) and Ppa, these groups gained 12.0 +/- 4.1, 4.6 +/- .3 and 4.0 + .3 gm/hr respectively (mean +/- SD). These results suggest that (1) spontaneous edema formation in this model was mediated by H/sub 2/O/sub 2/ or one of its products; (2) that the effects of these species were likely extracellular (since infused CAT probably remains extracellular); (3) thatmore » sustained anoxia inhibits the development of edema.« less

Physician antismoking advice has been shown to increase smoking cessation, particularly among patients who have medical problems or perceive themselves to be at risk. The present study tested three hypotheses: (a) providing 3 to 5 min of behavioral counseling regarding a cessation strategy would be more effective than simply warning the smoker to quit smoking; (b) smokers with abnormal pulmonary function would be more likely to comply with medical advice than would smokers with normal pulmonary function; and (c) that smokers with abnormal pulmonary function who receive behavioral counseling would be the group most likely to achieve prolonged abstinence. Asbestos-exposed smoking men undergoing screening in a mandated program for naval shipyard workers were categorized as having normal or abnormal pulmonary status on the basis of chest X ray and pulmonary function tests (PFT). They were then randomly assigned within PFT categories to receive either a simple warning or 3 to 5 min of behavioral cessation counseling from the physician who gave them the results of their pulmonary tests. Subjects' smoking status was evaluated at 3- and 11-month intervals following the physician intervention. Smokers who received behavioral counseling were more likely to quit and remain abstinent over the 11-month period (8.4% abstinent) than were smokers given a minimal warning (3.6% abstinent). Prolonged abstinence rates among abnormal PFT subjects (3.7%) did not differ from those of normals (5.9%). The group with normal PFT who received behavioral counseling achieved the highest level of abstinence (9.5%). Maintaining adequate physician compliance with the counseling protocol proved difficult; implications of this for future efforts are discussed.

As part of and as an adjunct to a longterm genetic and epidemiologic study of risk factors for chronic obstructive lung disease conducted at the Johns Hopkins Medical Institutions, we have been interested in examining the patterns of pulmonary function in different groups. In a study previously published, 1 Enjeti S Hazelwood B Permutt S Menkes H Terry P Pulmonary function in young smokers: male-female differences. Am Rev Respir Dis. 1978; 118: 667-676 Crossref PubMed Scopus (29) Google Scholar important male-female differences were noted in the pattern of pulmonary function observed in young smokers that led us to further examination of the pattern of change in pulmonary function in men and women under observation in the longterm genetic epidemiologic study. In the first study of young smokers our group observed that: 1) simple tests of lung function show clear differences between smokers and nonsmokers, and 2) that men seemed to respond differently to habitual cigarette smoking at an earlier stage than the women. In that study, 205 adults between the ages of 18 and 25 were classified into four groups according to sex and smoking status. Pulmonary function studies were performed using standard techniques. For purposes of this discussion it was observed that in men, tests of FEV1/FVC under conditions of breathing helium and oxygen clearly separated smokers from nonsmokers. In women no separation was detected. The clear separation between male smokers and nonsmokers was observed both under conditions of air and helium and oxygen when measurements of FEV3/FVC was considered. Again, however, no differences were observed in women. There was, however, a clear difference in the measured FEV3/FVC between smoking men and women, under conditions of breathing either air or helium and oxygen. Studies of the diffusing capacity for carbon monoxide in that population also revealed that the diffusing capacity was decreased to a greater extent in female rather than male smokers. Smoking habits did not account for the observed differences. The number of pack-years of smoking recorded in the questionnaire administered by a trained interviewer was not significantly different for male and female smokers. In addition, calculations of carboxyhemoglobin concentration estimated from the back pressure measurement in the steady state diffusing capacity study revealed that carbon monoxide levels were the same in both men and women smokers.

Forced expiration is the most widely used test for assessing pulmonary mechanics in man. For clinical purposes, results can be described in terms of the forced vital capacity (FVC) and the forced expiratory volume in 1 sec (FEV1). In order to provide a more complete description of forced expiration, additional parameters have been applied, e.g., flows at various lung volumes (flow volume loops) and the distribution of transit times during lung emptying (moments).

We, at the Johns Hopkins Medical Institutions, have been interested in risk factors that are associated with the development of chronic obstructive pulmonary disease (COPD). 1 Cohen BH et al. A genetic-epidemiologic study of chronic obstructive pulmonary disease. The Johns Hopkins Med J. 1975; 137: 95-104 PubMed Google Scholar In the longterm genetic-epidemiologic study described previously, we have shown that first-degree (1°) relatives of individuals with COPD have a significantly higher frequency of pulmonary function impairment than first-degree relatives of nopulmonary patients and that this difference persists when adjusted for multiple other risk factors. 2 Cohen BH et al. Risk factors in chronic obstructive pulmonary disease. Am J Epidemiol. 1977; 105: 223-231 PubMed Google Scholar

We have investigated the mechanisms involved in the inspiratory fall in left ventricular stroke volume (LVSV), utilizing a spontaneously breathing dog on right-heart bypass (RHBP). We have been able to control lung volume, pulmonary artery inflow, and right-heart volume (RHV). During Mueller maneuvers in one series, RHV was allowed to increase as pleural pressure (Ppl) fell; in a second series, changes in RHV were excluded. In both series LVSV fell significantly, associated with a significant rise in the transmural (relative to Ppl) aortic diastolic pressure, reflecting an increase in the effective LV afterload. The transmural left ventricular filling pressure did not fall, a fact inconsistent with decreased pulmonary venous return, causing the fall in LVSV. The LVSV fell significantly more when RHV was allowed to increase as when it was held constant with all other variables showing no statistical change. Thus, increases in both RHV and effective LV afterload are created by the inspiratory fall in Ppl and summate to decrease LVSV.

The results of pulmonary function testing and systematic medical history and epidemiologic data collection are reported for 20 persons with alpha 1-antitrypsin deficiency of Pi Z phenotype. The most common symptom, reported in 19 subjects (95 per cent), was dyspnea on exertion; 16 subjects (80 per cent) gave a history of wheezing, and 8 (40 percent) reported chronic cough and sputum production. The 8 women who had been pregnant reported a miscarriage rate of 29 per cent for all pregnancies. Respiratory symptoms and disease were commonly reported in the children of study subjects. Pulmonary function testing revealed abnormalities for 18 of 20 subjects, all of those 26 or more years of age. The test that was most frequently abnormal was the 1-sec forced expiratory volume expressed as a per cent of the forced vital capacity. All pulmonary function studies demonstrated a trend toward increased impairment with increased age, which was evident by the fourth decade. Within this group of persons having severe alpha1-antitrypsin deficiency, there was no correlation between serum concentrations of antitrypsin and subjective or objective indices of pulmonary disease. A group of 7 subjects who were incidentally found to have Pi Z alpha1-antitrypsin deficiency exhibited symptoms and pulmonary function abnormalities comparable to those of 13 subjects who were originally referred for known or suspected pulmonary disease. These data suggest that if interventions such as smoking cessation and occupational counseling are to be effective, they should be initiated before the fourth decade of life.

Results of certain tests of pulmonary function, including a questionnaire, single-breath N2 test of closing capacity, forced expiration, and diffusing capacity were significantly different in groups of male smokers and nonsmokers. The influence of age on these smoking-related changes of pulmonary function was evaluated. The analyses indicated that (1) some tests including number of symptoms; closing capacity, i.e., closing volume plus residual volume as a percentage of total lung capacity; residual volume as a percentage of total lung capacity; Phase III of the single-breath N2 test, and steady-state diffusing capacity (ml of CO/mm Hg - min) revealed significant differences between adjusted mean smoker and nonsmoker values but did not reveal differences associated with age. (2) Tests of forced expiration (1-sec forced expiratory volume/vital capapity, reciprocal of the maximal mid-expiratory flow, maximal flow at 50 per cent of vital capacity; and moments) however, revealed differences between smoker and nonsmoker means )adjusted and unadjusted), as well as increasing smoker-nonsmoker differences with increasing age. It is suggested that the first group of tests probably measured an all-or-none response that occurred with the onset of smoking and was not affected by duration of smoking. The second group of tests probably measured the effects of continued smoking and indicated increasing abnormality associated with longer exposure (years of smoking). Test showing age-related differences between smokers and nonsmokers may reflect cummulative, irreversible changes in pulmonary function to a greater extent than test that do not.