Idiopathic pulmonary haemosiderosis revisited.

Idiopathic pulmonary haemosiderosis is a rare cause of diffuse alveolar haemorrhage of unknown aetiology. It occurs most frequently in children, has a variable natural history with repetitive episodes of diffuse alveolar haemorrhage, and has been reported to have a high mortality. Many patients develop iron deficiency anaemia secondary to deposition of haemosiderin iron in the alveoli. Examination of sputum and bronchoalveolar lavage fluid can disclose haemosiderin-laden alveolar macrophages (siderophages), and the lung biopsy shows numerous siderophages in the alveoli, without any evidence of pulmonary vasculitis, nonspecific/granulomatous inflammation, or deposition of immunoglobulins. Contrary to earlier reports, corticosteroids alone or in combination with other immunosuppressive agents may be effective for either exacerbations or maintenance therapy of idiopathic pulmonary haemosiderosis.

Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in patients with COPD.

STUDY OBJECTIVE: To compare the efficacy and safety of ipratropium bromide reformulated with the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane (HFA)-134a (ipratropium bromide HFA) to that of the marketed ipratropium bromide inhalation aerosol (containing CFC) in patients with COPD. DESIGN: This was a randomized, double-blind, parallel-group, placebo-controlled, multicenter trial. The primary efficacy parameter was acute bronchodilator response. The primary end points were peak change in FEV(1) from baseline and area under the response-time curve. SETTING: Thirty-one clinical centers in the United States participated in this project. PATIENTS: A total of 507 patients with moderate-to-severe COPD were randomized, and 444 patients completed the trial. INTERVENTIONS: Twelve weeks of treatment four times daily with one of the following: ipratropium bromide HFA, 42 microg; ipratropium bromide HFA, 84 microg; HFA placebo; ipratropium bromide inhalation aerosol, 42 microg; or CFC placebo. MEASUREMENTS AND RESULTS: Patients in all active treatment groups had significant bronchodilator responses as shown by increases in mean FEV(1) from baseline of at least 15%. Bronchodilator response in all active treatment groups was also significantly more than their respective placebo treatments based on FEV(1), area under the time-response curve from 0 to 6 h, and peak response. FVC results were similar to those seen with FEV(1). There were no significant differences in adverse events, laboratory findings, or ECG findings among the treatment groups. CONCLUSIONS: Ipratropium bromide HFA, 42 and mgr;g, provided bronchodilation comparable to the marketed ipratropium bromide CFC, 42 and mgr;g, over 12 weeks of regular use.

Eosinophilic pneumonia as a presentation of occult chronic granulomatous disease.

We present a case of invasive pulmonary aspergillosis (IPA) in a previously healthy young woman who presented with what initially appeared to be an acute eosinophilic pneumonia. A second lung biopsy taken after treatment with steroids showed invasive Aspergillus with associated necrotizing granulomas, a pattern commonly found in chronic granulomatous disease (CGD). Both siblings, and by extrapolation, the patient, were actually found to have CGD. A review of the literature revealed other cases of presumed immunocompetent patients with IPA with presentations and lung histopathology similar to that of our patient. We conclude that chronic granulomatous disease presenting in the adult may be more common than previously assumed, and that patients previously presumed immunocompetent, but with granulomatous invasive pulmonary aspergillosis, may have chronic granulomatous disease. Furthermore, and most devastatingly in this case, the presentation may simulate a recently described steroid responsive acute lung disease, acute eosinophilic pneumonia.

Comparison of volume output from two different continuous nebulizer systems.

BACKGROUND: Continuous nebulization is a safe and practical method of administration of beta 2-adrenergic agonists during acute asthma. There are essentially two types of continuous nebulizer systems; one utilizes a large volume nebulizer and the other a small volume nebulizer attached to a constant volume infusion pump. OBJECTIVES: We compared the volume output characteristics of these two systems. METHODS: Study performed at Danbury Hospital. Both types of continuous nebulizers were reconstructed as reported in the literature and output monitored hourly for four hours. A total of nine nebulizers from each type of continuous nebulizer was evaluated, three from each of three different lots. RESULTS: The volume output of the large volume nebulizer ranged from 37.7 to 55.4 mL/h with a mean of 45.96 mL/h (P = .0001). Contrasts within the repeated measure ANOVA revealed that all pairwise contrasts in time were significant (P < .05) except for the 60 and 120 minute means. The volume output of the small volume nebulizer ranged from 15.0 to 16.6 mL/h with a mean of 15.88 mL/h. There was a significant difference in the mean volume output across time for the 60-minute value only. No other significant differences were found. CONCLUSION: These data suggest that the small volume nebulizer utilized in this manner for continuous nebulization is a more consistent delivery device than the large volume nebulizer. Further data are required on both actual drug output and mass median aerodynamic diameter of the particles generated by these nebulizers before one can recommend a particular system.

Continuous versus frequent intermittent nebulization of albuterol in acute asthma: a randomized, prospective study.

BACKGROUND: In acute severe asthma the optimal dose, frequency, duration and method of administration of beta-2 agonists is unknown. No study to date has evaluated the efficacy of high dose beta-2 agonists beyond the initial two hours. OBJECTIVE: (1) To determine whether high-dose continuous nebulization of albuterol (7.5 mg/h) is as safe and as efficacious as high-dose intermittent nebulization of albuterol (2.5 mg every 20 minutes) for four hours. (2) To evaluate whether there is a continual improvement using high dose therapy beyond two hours. METHODS: We devised a simple means of continuous nebulization calibrated to deliver 7.5 mg albuterol per hour. Twenty-two nonsmoking, patients with acute, severe asthma who presented to the emergency department with less than 60% predicted normal PEFR were randomized to either the continuous or intermittent group. All patients received intravenously 125 mg methyl prednisolone on initiation of the study. No theophylline was administered. Spirometry and vital signs were measured at baseline and every 30 minutes thereafter. Electrocardiograms were obtained on all patients and all patients had continuous cardiac monitoring. RESULTS: Both groups doubled their baseline spirometric values over the four-hour period (P < .0001). The FEV1 did not differ significantly between regimens at any time interval. Improvement from 120 minutes to 240 minutes was statistically significant (P < .0001). There was no significant difference in vital signs at the end of the study compared with baseline in either group, nor between the two groups at any time interval. CONCLUSION: High-dose continuous nebulization of albuterol is as safe and as efficacious as intermittent nebulization of albuterol in the early treatment of asthma in an emergency department. To our knowledge, this is the first study showing continued significant improvement beyond the initial two hours of therapy using high dose nebulized beta-2 agonists.

A comparison of inhaled ipratropium, oral theophylline plus inhaled beta-agonist, and the combination of all three in patients with COPD.

To evaluate the role of inhaled ipratropium bromide alone vs oral theophylline plus inhaled beta-agonist or the combination of all three in patients with stable COPD, the following double-blind, placebo-controlled study was conducted. Forty-eight patients with stable COPD (mean age, 61.8 years, with mean baseline FEV1 < 1.0 L) were randomized on four separate days to receive the following drug regimens: (1) theophylline tablets (dose previously determined to result in blood level of 12 to 18 mg/L), followed by inhaled albuterol (2 puffs via metered-dose inhaler [MDI]), followed by inhaled placebo (2 puffs via MDI); (2) oral placebo followed by ipratropium (2 puffs via MDI; 36 micrograms), followed by inhaled placebo; (3) oral theophylline, followed by albuterol, followed by ipratropium; or (4) oral placebo followed by two inhaled placebos. On study days, spirometry and heart rate were measured at time 0, 30 min, 60 min, and hourly for 6 h. The FEV1 peak change (liters) and area under the curve (liter x hours) for the treatment groups were compared. Ipratropium was more effective than placebo (p = 0.001 and p = 0.0078, respectively). The combination of albuterol and theophylline was superior to ipratropium alone (p = 0.001 and p = 0.0001, respectively), and all three drugs together were superior to the combination of albuterol and theophylline (p = 0.0373 and p = 0.0289), respectively; one-sided test of hypotheses). Peak heart rates were significantly higher for treatment groups compared with placebo groups (p = 0.0001). However, theophylline and albuterol and the combination of all three drugs resulted in greater peak heart rates than did ipratropium alone (p = 0.001). These data suggest that for patients with stable COPD, combination therapy with ipratropium (two puffs), theophylline, and albuterol (two puffs) is superior to ipratropium alone or the combination of theophylline and albuterol.

The tidal volume response to incremental exercise in COPD.

Patients with severe COPD often exhibit a ventilatory limit to exercise. This is associated with a shallow breathing pattern when compared with normal control subjects. It is unclear, however, what factors affect differences in breathing patterns within this patient population. To further investigate the tidal volume (VT) response to exercise in severe COPD, nine patients were recruited to undergo a maximal incremental exercise test. Pulmonary function tests, collection of expired gases, and continuous pulse oximetry were performed. As a group, the results were as follows (mean +/- SD): The FEV1 was 31 +/- 7 percent of predicted, the FRC was 143 +/- 18 percent of predicted, and the DCO was 47 +/- 15 percent of predicted. Exercise testing showed an oxygen consumption at peak exercise of only 44 +/- 9 percent predicted, a dyspnea index of 101 +/- 19 percent predicted, a heart rate at peak exercise of 75 +/- 12 percent predicted, a tidal volume at peak exercise (PKVT) of 1.23 +/- .35, a respiratory rate at peak exercise (PKfb) of 26 +/- 6, and an oxygen saturation at peak exercise (PKO2sat) of 96 +/- 4 percent. An anaerobic threshold (AT) occurred in seven of the nine patients at a mean of 31 +/- 8 percent predicted maximal oxygen consumption. Regression analysis showed the PKVT to be inversely correlated with the FEV1 (r = -0.76; p = 0.01) and the PKfb (r = -0.85; p = 0.003), while positively correlating with the FRC (r = +0.80; p = 0.01) and the PKO2sat (r = +0.69; p = 0.04). Additionally, there was a trend for the PKVT to be inversely related with the AT (r = -0.72; p = 0.06). In COPD, the more severe the obstruction and hyperinflation, the larger the VT response to exercise. This may serve to avoid a deleterious increase in autoPEEP by promoting a lengthening of the expiratory time. Furthermore, given the association of an earlier AT and a higher PKO2sat with a larger PKVT, this would suggest that such a response may minimize the effects of dead space and/or autoPEEP on O2 delivery (early AT).