Objective: To define the relationship between skin bruising (as well as other cutaneous manifestations) and inhaled corticosteroid (ICS) therapy vs placebo in subjects with COPD who were participating in a clinical trial. To explore the relationship between easy skin bruising and other systemic effects of ICS therapy, including adrenal suppression and loss of bone mineral density (BMD).Design: Double-blind, randomized, placebo-controlled clinical trial of triamcinolone acetonide (1200 jig daily) vs placebo in participants with mild-to-moderate COPD.Setting: Lung Health Study II, a clinical trial to assess the effect of ICS compared to placebo in 1,116 participants in 10 centers over > 3.5 to 4.5 years.Participants: A total of 1,116 smokers or recent ex-smokers with mild-to-moderate COPD (age range, 40 to 69 years; mean age, 56.3 years; 37.2% female).Measurements and results: Every 6 months, a structured questionnaire was administered to elicit reports of any bruising and/or skin rashes, slow healing of cuts or sores, or other skin changes. Compliance with inhaler use was assessed by canister weighing. A significantly higher proportion of ICS than placebo participants who complied with using their inhaler reported easy bruising (11.2% vs 3.5%, respectively) and the slow healing of skin cuts or sores (2.4% vs 0.5%, respectively). Older men in the ICS group with good inhaler compliance appeared to be at the greatest risk of bruising. In those participants undergoing serial measurements of adrenal function and BMD, no association was noted between skin bruising and either the suppression of adrenal function or the loss of BMD as systemic complications of ICS use.Conclusion: These findings indicate that moderate-to-high doses of ICSs result in an increased incidence of easy bruising and impairment in skin healing in middle-aged to elderly persons with COPD. No association was noted between skin bruising and other markers of systemic toxicity from the use of ICSs.

STUDY OBJECTIVE:Inhaled corticosteroids (ICS) are widely used in the treatment of COPD. One of the potential adverse effects of their use is the development of adrenal suppression. Our study aimed to determine the effects of ICS on adrenal function over 3 years of use in patients with COPD.METHODS:Two hundred twenty-one subjects were recruited from the 1,116 patients already enrolled in Lung Health Study II and were randomized to receive either triamcinolone, 1,200 microg, or placebo daily. Basal cortisol levels and cortisol levels at 30 min and 60 min following cosyntropin injection were measured at study entry and after 1 year and 3 years of participation.RESULTS:Basal cortisol levels in the placebo group were higher than in those receiving active drug at all time points and rose through the study period. There was no suppression of cortisol levels after cosyntropin stimulation at any study point in any subgroup.CONCLUSION:Use of inhaled triamcinolone, 1,200 microg/d, over 3 years does not suppress baseline adrenal function or diminish adrenal responsiveness to cosyntropin stimulation.

This paper evaluates the hypothesis that Black smokers will respond differently than Whites to a smoking cessation intervention program where no adjustments are made in recognition of cultural differences. The responses of Black smokers who were recruited into the Lung Health Study (LHS) to the smoking cessation intervention are described. Black quit rates are compared with those of Whites. The LHS enrolled 5887 men and women smokers, aged 35-60 years, of whom 3923 were randomized to a group cessation intervention and 1964 to usual care. Blacks and Whites from six clinics who had complete covariate data (200 Blacks and 2868 Whites) were compared on baseline smoking characteristics and subsequent smoking cessation outcomes. Logistic models were constructed to adjust for baseline smoking variables and demographic characteristics to evaluate the effect of treatment group on smoking cessation among Blacks and Whites. At baseline, Blacks reported smoking fewer cigarettes than Whites, but had higher mean levels of salivary cotinine. The adjusted odds ratio of quitting at 1 year for the smoking intervention group vs. the usual care group was 1.48 for Blacks and 5.99 for Whites. This difference between Blacks and Whites was highly significant (p = 0.002). Across 5 years, the adjusted odds ratios of quitting were 1.87 for Blacks and 3.34 for Whites (p = 0.06). Although the treatment effect was stronger for Whites than for Blacks, over the 5 years of the study there was a significant treatment effect for Blacks. Indicators of physical dependence on nicotine at baseline were inconsistent in indicating whether Blacks were more dependent. We conclude that Blacks and Whites differed significantly in their response to the LHS group smoking intervention program.

BACKGROUNDChronic obstructive pulmonary disease (COPD) results from a progressive decline in lung function, which is thought to be the consequence of airway inflammation. We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline.METHODSWe enrolled 1116 persons with COPD whose forced expiratory volume in one second (FEV1) was 30 to 90 percent of the predicted value in a 10-center, placebo-controlled, randomized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily. The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator. The secondary outcome measures included respiratory symptoms, use of health care services, and airway reactivity. In a substudy of 412 participants, we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment.RESULTSThe mean duration of follow-up was 40 months. The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group (44.2+/-2.9 vs. 47.0+/-3.0 ml per year, P= 0.50). Members of the triamcinolone group had fewer respiratory symptoms during the course of the study (21.1 per 100 person-years vs. 28.2 per 100 person-years, P=0.005) and had fewer visits to a physician because of a respiratory illness (1.2 per 100 person-years vs. 2.1 per 100 person-years, P=0.03). Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months (P=0.02 for both comparisons). After three years, the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group (P < or = 0.007).CONCLUSIONSInhaled triamcinolone does not slow the rate of decline in lung function in people with COPD, but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems. These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density.

Subjects greater than or equal to 18 yr of age with serum alpha(1)-antitrypsin (alpha(1)-AT) levels less than or equal to 11 mu M or a ZZ genotype were followed for 3.5 to 7 yr with spirometry measurements every 6 to 12 mo as part of a National Heart, Lung, and Blood Institute Registry of Patients with Severe Deficiency of Alpha-1-Antitrypsin. Among all 1,129 enrollees, 5-yr mortality was 19% (95% CI: 16 to 21%). In multivariate analyses of 1,048 subjects who had been contacted greater than or equal to 6 mo after enrolling, age and baseline FEV1% predicted were significant predictors of mortality. Results also showed that those subjects receiving augmentation therapy had decreased mortality (risk ratio [RR] = 0.64, 95% CI: 0.43 to 0.94, p = 0.02) as compared with those not receiving therapy. Among 927 subjects with two or more FEV1 measurements greater than or equal to 1 yr apart, the mean FEV1 decline was 54 ml/yr, with more rapid decline in males, those aged 30 to 44 yr, current smokers, those with FEV1 35 to 79% predicted, and those who ever had a bronchodilator response. Among all subjects, FEV1 decline was not different between augmentation-therapy groups (p = 0.40). However, among subjects with a mean FEV1 35 to 49% predicted, FEV1 decline was significantly slower for subjects receiving than for those not receiving augmentation therapy (mean difference = 27 ml/yr, 95% CI: 3 to 51 ml/yr; p = 0.03). Because this was not a randomized trial, we cannot exclude the possibility that these differences may have been due to other factors for which we could not control.

A 24-year-old man presenting with fever, rash, and myalgias subsequently developed hypercapnic respiratory failure and severe limb muscle weakness. Muscle biopsy revealed eosinophilic myositis, due to the ingestion of large quantities of L-tryptophan as a dietary supplement. Complete recovery occurred with corticosteroid administration. Significant involvement of the respiratory muscles can be a predominant feature of this newly described disease entity.

Of approximately 6000 admissions to the Henry Ford Hospital medical ICU between October 1969 and September 1984, 61 (1%) had active tuberculosis (TB). Forty-three (70%) of these 61 had acute respiratory failure (ARF). TB was considered to be the sole cause of ARF in 12 and contributory in 31. Eighteen patients with TB but without ARF were admitted for treatment of other critical illnesses. Alcoholism was present in 31 (51%) of the TB patients. Only one of 12 whose ARF was caused primarily by TB had a history of known TB at the time of admission. Important factors contributing to ARF in TB patients included Gram-negative pneumonia and/or sepsis, chronic obstructive pulmonary disease, prior TB with anti-TB medication noncompliance, and malignancy. Six patients were not suspected of having TB when admitted to the medical ICU; three patients who had not been treated for TB were found to have TB on autopsy. The inhospital mortality rate for all patients with TB requiring intensive care was 67%, but was 81% in those with ARF.

Patients presenting with inoperable non-small cell carcinoma of the lung and major symptomatic bronchial obstruction were treated initially with debulking of the airways by YAG laser, followed by conventional external-beam radiotherapy. The former method was used to minimize postobstructive pneumonitis or respiratory failure (or both) that often complicates major brochial obstruction and also to lessen the burden of tumor to be treated by radiotherapy. The preliminary results of 19 patients treated in this manner are reported, emphasizing the impact of this combined method on morbidity and mortality.

We investigated the role of decreased theophylline protein binding as a possible explanation for observed decreases in total theophylline concentrations (TC) in acutely-ill patients (AIP). Multiple blood samples were obtained from nine AIP with underlying chronic obstructive pulmonary disease (COPD) and from 13 stable COPD patients. The mean albumin concentration +/- SD was 2.7 +/- .61 mg/dl in the AIP vs 4.0 +/- 0.52 mg/dl in the stable COPD patients (p less than 0.005). Total (TC) and unbound theophylline concentrations (UTC) were determined. Theophylline protein binding was assessed at room temperature by centrifugal ultrafiltration of the patients' sera. The TC was 13.7 +/- 4.8 micrograms/ml in the stable COPD patients vs 11.8 +/- 4.1 micrograms/ml in the AIP although the mean dose was larger (17.21 +/- 5.41 vs 10.7 +/- 4.09 mg/kg/day of theophylline) in the AIP (p less than 0.005). There was no difference in UTC between the two groups (7.4 +/- 2.5 micrograms/ml and 8.1 +/- 2.6 micrograms/ml); however, the unbound fraction was higher in the AIP (p less than 0.005). We conclude that theophylline protein binding appears altered in AIP and that the altered binding relates predominantly to the severity of the clinical illness.

The authors report the case of a patient with long-standing Sézary syndrome who developed the acute onset of bilateral pulmonary infiltration, severe hypoxemia, and hypotension. Initial diagnostic considerations centered around infection, but an open-lung biopsy revealed “mycosis fungoides” without evidence of an infectious process. The patient showed striking improvement when given vincristine and cyclophosphamide, but ultimately died 3 months later of a nonpulmonary catheter-related infection. This rare clinical association stresses the value of open lung biopsy as a diagnostic measure even in desperately ill individuals.

Some patients with cancer and others with benign lesions which obstruct the central airways (larynx, trachea, major bronchi) can be treated with a laser. Ninety-nine patients were considered for treatment during the first 18 months of experience with a YAG (yttrium aluminum garnet) laser at Henry Ford Hospital; 55 patients were treated 82 times. Results were satisfactory (surgery was avoided) in eight of ten patients with benign lesions. Satisfactory results (doubling of airway size with relief of dyspnea/drainage of obstructive pneumonia) were obtained in 12 of 13 patients with bronchogenic carcinoma managed initially with the laser, and in 22 of 32 (69 percent) patients with recurrent malignancies. There were five minor and seven major complications, including two deaths. We conclude that laser treatment can relieve central airways obstruction with its associated symptoms of dyspnea and infection. Avoidance of complications requires a skillful approach, careful anesthetic management, and availability of back-up posttreatment intensive care.