Suetaro Watanabe

Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease: A 90-day multi-center study

The short- and long-term efficacy and safety of an inhaled quaternary ammonium anticholinergic agent, ipratropium bromide, and a beta agonist aerosol, metaproterenol, were compared in 261 nonatopic patients with chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, 90-day, parallel-group trial. On three test days-one, 45, and 90-mean peak responses for forced expiratory volume in one second and forced vital capacity and mean area under the time-response curve were higher for ipratropium than for metaproterenol. Clinical improvement was noted in both treatment groups, especially during the first treatment month, with persistence of improvement throughout the remainder of the study. Side effects were relatively infrequent and generally mild; tremor, a complication of beta agonists, was not reported by any subject receiving ipratropium. These results support the effectiveness and safety of long-term treatment with inhaled ipratropium in COPD.

The acute effects of chrysotile asbestos exposure on lung function

Abstract Lung function was determined in 23 men 1.5 months after an intense 5-month exposure to chrysotile asbestos using spirometry, plethysmography for determination of lung volumes and specific conductance, single breath nitrogen washout for determination of closing volume, and rest and postexercise arterial blood gas analysis. Although no man showed evidence of restriction, 12 of the 23 had documented airflow obstruction. Eight months following exposure, 16 of the 23 had a repeat pulmonary evaluation. This included the repetition of all previous testing and determination of the diffusion capacity for carbon monoxide and pulmonary compliance. Three men developed airflow obstruction, as determined by the closing volume, during the interval of study. Seventeen of the 23 had airflow obstruction documented on either the initial or follow-up study. Of these 17, 12 were nonsmokers, current light smokers (less than 10 pack years), or ex light smokers. It is concluded that acute intense chrysotile asbestos exposure causes airflow obstruction.

Pathologic patterns of chronic obstructive pulmonary disease in patients with normal and deficient levels of alpha1 antitrypsin

Abstract Twenty-nine patients with chronic obstructive pulmonary disease (COPD), selected on the basis of their alpha 1 antitrypsin (AAT) phenotype or trypsin inhibitory capacity (TIC), were studied by clinical and physiologic methods. Six were homozygous, 10 were heterozygous and 13 were normal with respect to their AAT levels. Spirometry, lung volume and diffusing capacity measurements indicated that the extent of pulmonary disease was greater in the patients with homozygous AAT deficiency as compared to the other groups. Quantitative measurements of regional ventilation and perfusion were made using xenon 133 and the results were evaluated by statistical technics. Two different methods of discriminant analysis of the regional ventilation and perfusion data clearly showed the three groups of patients to be significantly different from each other. Since the heterozygous AAT deficient patients had a pattern of disease which distinguished them from patients with both severely deficient and normal AAT levels, it is concluded that heterozygosity for AAT is an important factor in the development of COPD.

Characterization of bleomycin lung injury by nuclear magnetic resonance: Correlation between NMR relaxation times and lung water and collagen content

The response of the NMR relaxation times (T1, CPMG T2, and Hahn T2) to bleomycin‐induced lung injury was studied in excised, unperfused rat lungs. NMR, histologic, and biochemical (collagen content measurement) analyses were performed 1, 2, 4, and 8 weeks after intratracheal instillation of saline (control lungs) or 10 U/kg bleomycin sulfate. The control lungs showed no important NMR, water content, histologic, or collagen content changes. The spin‐spin relaxation times for the fast and intermediate components of the CPMG decay (T2f and T2i, respectively) increased 1 week after bleomycin injury (acute inflammatory stage) and then progressively decreased during the following 2–8 weeks (i.e., with the development of the chronic, fibrotic stage of the injury). The slow component (T2s) showed no significant changes. The response of T1 and the slow component of the Hahn T2 was, on the whole, similar to that of CPMG T2f and T2i. T1 changes were very small. Lung water content increased 1 week after injury. Histologic and biochemical assessment of collagen showed that collagen content was close to control at 1 week, but markedly increased at 2, 4, and 8 weeks. T1 and T2 data were directly correlated with lung water content and inversely correlated with collagen content. Our results indicate that NMR relaxation time measurements (particularly T2) reflect the structural changes associated with bleomycin injury. The prolonged T2 relaxation times observed in the acute stage are related to the presence of edema, whereas the subsequent decrease in these values marks the stage of the collagen deposition (fibrotic stage). CPMG‐T2 and Hahn‐T2 measurements can be valuable as a potentially noninvasive method for characterizing bleomycin‐induced lung injury and pathologically related lung disorders. Magn Reson Med 47:246–256, 2002.

Thesaurosis—from hairspray exposure—a nondisease: Validation studies of an epidemiologic survey of cosmetologists

Abstract In a previously reported epidemiologic survey, 25 of 475 cosmetologists and 21 of 569 noncosmetology control subjects demonstrated one or more of three abnormalities (abnormal chest X ray, reduction of forced vital capacity, or diffusion capacity of the lung) that might indicate the presence of “thesaurosis,” a previously described disease attributable to lung storage of components of hair spray. This report describes the results of examining these subjects and equal numbers of matched control subjects approximately 2 years after the original survey. The original survey X rays were reread by two experienced readers of chest X rays and responders received the following examinations: respiratory questionnaire, chest X ray, spirometry, diffusing capacity of the lung for carbon monoxide, and static pulmonary compliance. With one exception, the responding cosmetologists continued their occupation up to the time of reexamination. Neither the chext X-ray findings nor the results of pulmonary function testing substantiate the concept that there is such a disease as thesaurosis from hairspray exposure.

Informative Value of Simple Multibreath Nitrogen Washout Measurements for Clinical and Research Purposes

Some simple multibreath nitrogen washout indexes quantifying inspired gas distribution and ventilatory efficiency were obtained in a group of patients with mild to advanced chronic obstructive pulmonary disease (COPD) and studied in their relationships with routine pulmonary function tests. The indexes (lung clearance index (LCI), mixing ratio (MR) and data obtained by graphic analysis of the washout curve) were correlated with spirometric, pulmonary mechanics and arterial blood gas measurements, but only 8-38% of the interindividual variation in these indexes was explained by the above routine tests. An additional 5-13% of the variation was explained by the washout tidal volume (VT); this finding may reflect changes in gas distribution with VT and/or the influence of the dead space on ventilatory efficiency. Our data indicate that, in patients with COPD, nitrogen washout indexes tend to change in parallel with routine pulmonary function tests, reflecting the severity of the disease; these indexes also contain specific information (in addition to that provided by routine physiologic tests), presumably related to the distribution and efficiency of ventilation. Nitrogen washout measurements may thus represent a helpful adjunct to routine pulmonary function testing; LCI and MR appear to be particularly convenient for practical purposes because of their simplicity, and an informative content comparable with that of more complex indexes.

Pulmonary Resistance and Dynamic Compliance as Functions of Respiratory Frequency

The behavior of pulmonary resistance (RL) and that of dynamic compliance (Cdyn) as functions of respiratory frequency (f) were compared in normal subjects and in patients with chronic obstructive pulmonary disease (COPD). Although both RL and Cdyn varied with f in most COPD patients and in some normal subjects, Cdyn appeared to be more sensitive than RL to variations of frequency; no significant changes in RL could be demonstrated in subjects in whom Cdyn was frequency dependent. The degree of frequency dependence of Cdyn was correlated with the severity of respiratory impairment (as quantified by conventional pulmonary function tests); in contrast, RL was not detectably frequency dependent in some subjects with advanced COPD. Compared with Cdyn, RL was more commonly nonlinearly related to respiratory frequency, often increasing at high breathing rates. Our results indicate that changes in RL with frequency are less predictable and more difficult to detect than the corresponding changes in Cdyn.

The Role of the Pulmonary Function Laboratory in Patients with Bronchial Asthma

Spirometry is a dynamic test that provides the best assessment of obstructive airway disease. The most useful value that the spirogram provides is the maximum volume of air that can be expelled with a forced expiration following a maximal inspiratory effort, the FEV1. Lung volume measurements are static studies and are less useful in assessing airway obstruction, but can demonstrate the presence of pulmonary overinflation. The carbon monoxide diffusing capacity can help distinguish between asthma and emphysema in patients that smoke. Arterial blood gas studies can assess the consequences of bronchospasm and provide a guide for hospitalizing patients with asthma exacerbation. Nonspecific bronchoprovocation challenge testing with methacholine or other agents, may help diagnose asthma when the clinical picture is unclear. Bronchoprovocation challenge testing using specific agents can help diagnose asthma because of substances in the work place. Exercise studies can evaluate the patient as a “whole” and can distinguish between dyspnea caused by respiratory diseases or dyspnea caused by cardiac disease and/or deconditioning. Exercise studies can document exercise induced bronchospasm and can evaluate the benefits of a rehabilitation program for the patient limited by asthma. Standardization of technique and rigid quality control are an absolute necessity in any pulmonary laboratory.