Lack of effectiveness of magnesium in chronic stable asthma. A prospective, randomized, double-blind, placebo-controlled, crossover trial in normal subjects and in patients with chronic stable asthma.

BACKGROUND: Magnesium sulfate has been helpful in the treatment of acute exacerbations of asthma. We hypothesized that magnesium would also be an effective bronchodilator in patients with chronic stable asthma. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled, crossover trial in 15 patients with chronic, stable asthma and 10 nonasthmatics. On study day 1, spirometry and albuterol challenge were used to confirm the presence of asthma according to American Thoracic Society criteria. On study day 2, subjects received intravenous magnesium sulfate (2 g) or placebo (saline). On study day 3, subjects were crossed over to receive the other drug. Spirometry was performed before, during, and after drug or placebo administration. Circulating ionized magnesium concentrations were determined before and after intravenous magnesium or placebo administration. RESULTS: Magnesium infusion caused no statistically significant changes in forced expiratory volume in 1 second (mean +/- SEM, 1.92 +/- 0.13 L before, 1.98 +/- 0.12 L during, and 2.01 +/- 0.14 L after magnesium administration), forced vital capacity (mean +/- SEM, 3.44 +/- 0.25 L before, 3.60 +/- 0.26 L during, and 3.59 +/- 0.25 L after magnesium administration), or maximum forced expiratory flow rate (mean +/- SEM, 5.42 +/- 0.44 L/second before, 5.46 +/- 0.46 L/second during, and 5.57 +/- 0.49 L/second after magnesium administration). Placebo caused no changes in these three physiologic variables. CONCLUSION: Magnesium is not effective as a bronchodilator in chronic, stable asthmatics or in normal non-asthmatic adults.

The treatment of neurosarcoidosis with cyclosporine.

Six patients with refractory neurosarcoidosis were enrolled in a 12-month open-label trial to investigate the safety and efficacy of cyclosporine therapy. Patients were stabilized on a corticosteroid dose, randomized to a low-dose or high-dose cyclosporine group (with appropriate target whole blood cyclosporine levels) for 6 months, and assessed by prospectively defined studies. The corticosteroid dose was adjusted as clinically tolerated. We found that the corticosteroid dose could be lowered to 30% to 58% of the initial stabilization dose in conjunction with cyclosporine therapy, at the time of maximal clinical and laboratory improvement. However, four patients deteriorated while using corticosteroids and cyclosporine; one of these patients died. At the time of clinical deterioration, the prednisone dose ranged from 6 to 22.5 mg daily (or the equivalent). No serious toxic effects developed from cyclosporine therapy. Cyclosporine treatment is a reasonably safe and effective adjunct to corticosteroid therapy for patients with refractory neurosarcoidosis, although clinical deterioration can occur despite combination therapy.

Sarcoidosis.

Sarcoidosis continues to be a disease defined descriptively rather than by etiology. Bronchoalveolar lavage has brought new understandings of the pulmonary inflammatory process and its pathogenesis and defects in immunoregulation. Much is known of the clinical characteristics of sarcoidosis, its diagnosis and management. Spontaneous remissions are common, but when treatment is required, the response to corticosteroids is often dramatic, although long-term treatment may be required. The appropriate use of corticosteroids is discussed fully, as are special clinical problems.

Serial lung function testing in patients treated with amiodarone: a prospective study.

PURPOSE: Amiodarone has proven to be effective in many cases of cardiac arrhythmias, refractory ventricular tachycardia, and ventricular fibrillation. Pulmonary toxicity is a possible side effect of the drug, with a reported incidence of 2 to 15 percent per year. To determine the effect of amiodarone on lung function, we prospectively studied serial lung function tests in a cohort of 91 patients with refractory cardiac arrhythmias treated with this agent. PATIENTS AND METHODS: Spirometry and carbon monoxide diffusing capacity (DLCO) were measured at zero, three, six, 12, 18, and 24 months, with a mean follow-up of 351 days. RESULTS: For the whole population taking a mean dose of amiodarone of 367 mg daily (range: 136 to 512 mg), there was no accelerated rate of decline in spirometric indices or DLCO. Analysis of lung function changes by multivariate analysis demonstrated that an accelerated decline in DLCO values occurred in elderly patients (p less than 0.05) but not in patients with pre-existing lung disease or cigarette smokers. In four patients (4.5 percent), clinical evidence of amiodarone pulmonary toxicity developed that was associated with a fall in DLCO of greater than 20 percent. All four patients recovered after the drug was stopped. Another 15 patients, without clinical evidence of pulmonary toxicity, had a sustained decline in DLCO of greater than 20 percent. These 15 patients remained asymptomatic over the next 11 months without interruption of therapy. A greater than 20 percent fall in DLCO was a sensitive test for clinically evident amiodarone pulmonary toxicity, but had a positive predictive value of only 21 percent. CONCLUSION: An isolated fall in DLCO, in the absence of clinical evidence of toxicity, does not necessitate stopping amiodarone. An unchanged DLCO value appears to be a reliable negative predictor of pulmonary toxicity.

Longitudinal study of chronic sarcoidosis with low-dose maintenance corticosteroid therapy. Outcome and complications.

A series of 181 patients with chronic persistent sarcoidosis for more than 5 years have been reviewed, with a mean follow-up period of 14 years, and 77% followed for more than 10 years. Efforts to identify more white patients meeting the criteria of such persistent disease were unsuccessful. Seventy-eight percent were black, and 69% were women. Pulmonary disease was the major manifestation in 70% and was present in 88%. The early major disease feature predicts the nature of the long-term manifestation in 94%. Ninety-four percent were treated with prednisone, with 63% for more than 5 years. Fifty-three percent required continued treatment, and of those receiving continued treatment, 91% were maintained on doses of no more than 15 mg daily and 65% on no more than 10 mg of prednisone daily. Relapses were frequent as prednisone was withdrawn, occurring at least once in 75% and several times in 51%. Low-dose prednisone treatment with 5-15 mg daily provides significant benefit. A mean treatment period of 8 years was observed (range: 10 days to 24 years). The benefits of treatment greatly exceed the infrequent complications. In Baltimore, chronic sarcoidosis with persistent disease seems to be more frequently encountered in black patients than in white patients.

Advances in the diagnosis and treatment of broncholithiasis.

In order to determine the present clinical spectrum of broncholithiasis and the impact that chest computed tomographic (CT) scans, laminograms , and fiberoptic bronchoscopy ( FOB ) have had on the diagnosis and treatment of this entity, we reviewed our experience between 1970 and 1982. Nineteen patients were identified with this diagnosis. Cough, hemoptysis, and obstructive pneumonia were the most common presentations. Lithoptysis occurred in only 3 patients. The chest radiographic findings were nonspecific, but in 8 of the 19 patients, laminograms or chest CT scans helped establish the diagnosis; FOB was performed on 18 patients and was abnormal in each case, with 8 intrabronchial calcifications identified. However, FOB has limited therapeutic indications in this disorder. Depending on the patient's clinical status and underlying lung disease, observation, bronchoscopic removal of the stone, or surgical resection may be indicated.

Bilateral diaphragmatic paralysis following topical cardiac hypothermia.

Topical cardiac hypothermia has been shown to be a safe and effective means of providing protection for the ischemic myocardium during aortic cross-clamping. We report herein two cases of postoperative bilateral diaphragmatic paralysis which we believe resulted from hypothermic injury to the phrenic nerves. After open-heart surgery, both patients experienced prolonged weaning from assisted ventilation and severe orthopnea. Return of normal diaphragmatic and phrenic nerve function was demonstrated in one patient ten months after surgery. Failure to correctly interpret the respiratory failure and orthopnea led to confusion and erroneous types of therapy. Awareness of this complication should lead to improved care and postoperative management of patients.

Cholelithiasis in adult cystic fibrosis.

The clinical picture of adult cystic fibrosis is usually dominated by respiratory failure. Hepatic dysfunction occurs commonly, but symptomatic cholelithiasis is a rarely reported complication of the disease. This case of common duct obstruction emphasizes the broad spectrum of sequelae that may be expected in this newly emerging population of adults with cystic fibrosis.

Pulmonary function studies in diffuse pulmonary North American blastomycosis.

Detailed pulmonary function studies were performed on 2 patients with diffuse pulmonary North American blastomycosis before and after therapy. Our studies showed a significant increase in lung restriction, stiffness, and small airways obstruction, which completely resolved with therapy. We conclude that adequate therapy, even in the presence of extensive disease, results in both clinical and physiologic recovery.

Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients.

The efficacy of corticosteroid treatment in the prophylaxis of the fat embolism syndrome was evaluated in a prospective, randomized, double-blind study of high-risk patients with long-bone fractures. Using a set of objective diagnostic criteria, we saw a significant difference in the incidence of the syndrome between corticosteroid- (0 of 21) and placebo-treated patients (9 of 41) (p less than 0.05). There were no complications related to corticosteroid treatment. No routine laboratory or physical findings reliably predicted the development of the fat embolism syndrome except petechial rash, which occurred only in 5 placebo-treated patients who developed the syndrome. Complement activation was present in all patients studied who had the syndrome (5 of 27) but also in many patients who did not meet our diagnostic criteria, suggesting a multifactorial cause. These data support the prophylactic value of corticosteroid treatment in patients at high risk for the fat embolism syndrome, particularly if several unfavorable predictors are present.

Rapid diagnosis of Legionnaires' disease by bronchoalveolar lavage.

Legionella pneumophila has, in recent years, emerged as a common pulmonary pathogen in the normal and immuno-compromised patient (ICP). Making a specific etiologic diagnosis of pneumonia in the latter group is a common clinical dilemma often complicated by poor specimen availability and risks of invasive procedures. Improved staining and isolation techniques for L pneumophila would suggest that early diagnosis could be possible if adequate specimens were available. This report summarizes our experience with bronchoalveolar lavage (BAL) with which we have diagnosed L pneumophila in eight immunocompromised patients, well in advance of more traditional methods. On the basis of this experience, we would advocate early BAL in the ICP as a rapid, safe, moderately sensitive and specific diagnostic test to aid in the identification of L pneumophila.

Changes in pulmonary diffusing capacity and closing volume after running a marathon.

The purpose of this study was to evaluate changes in lung function after running a marathon. Pulmonary function tests were administered to 8 men before, immediately after, and the day following competition (mean run time = 3 hr 30 min). Subjects completed maximum expiratory flow volume maneuvers breathing air and 80% He/20% O2. Lung volumes were determined by N2 washout and single breath He dilution. Closing volumes (CV) were determined using a single breath O2 test. Pulmonary diffusing capacity (DLCO), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (DM) were measured with the single breath technique. There were no changes in lung volumes or flow rates, except for an increase in FEV1, after the marathon. The He/O2 delta Vmax50, delta Vmax25, and isoflow values were similar pre- compared to post-race. There were significant decreases, however, in DLCO, DM and increases in CV post-race. Vc remained similar to pre-race values. These results suggest that small airways obstruction does not occur after a marathon. The significant increase in alveolar-capillary membrane resistance, however, may reflect the occurrence of subclinical edema. Such a change would decrease lung elastic recoil and could explain the increase in CV.

Airway closure and trapped gas during low volume breathing.

We used a plethysmographic technique to estimate the trapped gas volume (TGV) in seven normal subjects after breathing air or O2 normally at functional residual capacity (FRC-air, FRC-O2) and near residual volume (RV) with small breaths (LVB-air, LVB-O2). If airway closure occurs, lung units subtended by closed airways would tend to collapse as TGV is absorbed; rapidly if the gas is O2 and slowly if it is air. Both inspiratory and expiratory quasi-static and static pressure-volume curves after LVB-O2 for 180 sec demonstrated a shift to the right and increased hysteresis, reduced vital capacity (VC) and significantly increased transpulmonary pressures at 25% and 50% control VC (PL25, PL50) as compared with those of FRC-O2 controls (P less than 0.01-P less than 0.001). Three VC breaths reversed these changes which suggested that they were related to atelectasis. The absolute plethysmographic RV level decreased and was also restored after three VC breaths. We used this reproducible decrease in RV level to represent the absorbed TGV (delta TGV). The delta TGV after LVB-O2 (180 sec) was significantly greater than that after LVB-air (P less than 0.001) or FRC-O2 (P less than 0.001). There was a significant correlation between the increase of delta TGV (DTGV) and the increase of PL25 (delta PL25) (P less than 0.01). The delta TGV after FRC-O2 was 128.6 +/- 50.3 ml (1.61 +/- 0.63% of TLC) and the maximal delta TGV after LVB-O2 (180 sec) averaged 504.3 +/- 40.5 m (7.5 +/- 0.37% TLC). The significant increase in delta TGV near RV during O2 as compared to air breathing is best explained by reversible atelectasis and further supports the concept of dependent airway closure at low lung volumes.

Mechanism of production of crackles after atelectasis during low-volume breathing.

We compared the effects of shallow breathing of air (LVB-air) and oxygen (LVB-O2) at low lung volumes (below closing capacity) and tidal breathing at FRC (FRC-air, FRC-O2) on the production of crackles in 5 normal volunteers. Two microphones were attached on the right posterior chest wall in the midclavicular line 10 and 20 cm from the apex of the right lung, respectively (M10 and M20), to record crackles during various breathing maneuvers. We found that after LVB-air and LVB-O2, there were changes in residual volume as measured by the body plethysmograph. Both inspiratory and expiratory limbs of the quasi-static pressure volume curve were shifted to the right. Occasionally, some subjects coughed after LVB-air and/or LVB-O2. Inspiratory crackles occurred mostly at the upper third of vital capacity (VC) after LVB-air and LVB-O2 and were confined almost exclusively to the dependent lung zones (M20). The inspiratory transpulmonary pressure at 25% (PL25) and 50% (PL50) of VC correlated with the volume of trapped gas that was absorbed (delta Vtg) (p less than 0.001 and p less than 0.001, respectively). The quantity of crackles correlated with delta Vtg (p less than 0.01). We conclude that during low lung volume breathing airways in the dependent lung regions are closed. There is absorption of trapped oxygen which causes reversible atelectasis. Upon reinflation, inspired air will go to the lung regions with open airways first and subsequently to the closed dependent regions, producing crackles recorded by the M20 microphone at the upper third of VC. The crackles are produced by inflation of atelectatic lung.