Controlled trial of two formulations of cromolyn sodium in the treatment of asthmatic patients > or = 12 years of age. Intal Study Group.

STUDY OBJECTIVES: This multicenter, randomized, double-blind, placebo-controlled, parallel study compared the efficacy and safety of the hydrofluoroalkane (HFA) formulation of cromolyn sodium metered-dose inhaler (MDI) with the chlorofluorocarbon (CFC) formulation in asthmatic patients > or = 12 years old over a 12-week period. DESIGN: Stable asthmatics using only currently marketed cromolyn sodium and as-needed inhaled beta2-agonists were randomly assigned to treatment with HFA cromolyn sodium, CFC cromolyn sodium, or placebo, administered as two inhalations (2 mg) qid for 12 weeks. Prior to randomization, all patients were required to meet minimum symptom and/or pulmonary function test criteria after discontinuation of cromolyn sodium. Efficacy was assessed by changes in daily symptom scores, albuterol use, peak expiratory flow, pulmonary function measurements, and overall opinions of effectiveness. RESULTS: A total of 280 patients in 29 centers were randomly assigned to treatment with HFA cromolyn sodium (n = 94), CFC cromolyn sodium (n = 91), or placebo (n = 95). Patients treated with the HFA formulation of cromolyn sodium demonstrated a 28 to 33% improvement over placebo for all symptom scores (p < 0.05) and a 35% improvement over placebo in the use of albuterol MDI (p < 0.05). The patients' opinions of overall effectiveness favored HFA cromolyn sodium (p = 0.011) and CFC cromolyn sodium (p = 0.006) over placebo. The investigators' opinions indicated a statistically significant difference favoring CFC cromolyn sodium compared with both placebo (p < 0.001) and HFA cromolyn sodium (p = 0.042). No statistically significant differences existed among groups in the incidence of treatment-related adverse events. CONCLUSION: The HFA formulation of cromolyn sodium MDI is a well-tolerated and effective treatment for asthma patients > or = 12 years old. The safety and efficacy profile of the HFA formulation is comparable to that of the CFC formulation.

Evaluation of a non-chlorofluorocarbon formulation of cromolyn sodium (Intal) metered-dose inhaler versus the chlorofluorocarbon formulation in the treatment of adult patients with asthma: a controlled trial.

BACKGROUND: Cromolyn sodium is a nonsteroidal inhaled antiinflammatory agent for the treatment of asthma. As with other pressurized aerosol medications, the metered-dose inhaler (MDI) formulation currently contains chlorofluorocarbon (CFC) propellants. Because of their harmful effects on the environment CFCs are now generally banned from production and use. Alternative propellants under production for MDIs include derivatives of hydrofluoroalkane (HFA). This study uses HFA-227 in an MDI formulation of cromolyn sodium. OBJECTIVES: The objectives of the study were (1) to examine the efficacy and safety of an HFA formulation of cromolyn sodium (Intal) MDI and (2) to compare the HFA formulation with the CFC formulation. METHODS: A multicenter, randomized, double-blind, placebo-controlled, parallel study with two active groups (HFA-cromolyn sodium [n = 113] and CFC-cromolyn sodium [n = 107]) and a placebo-treated group (n = 105). RESULTS: Patients treated with either formulation of cromolyn sodium MDI showed a statistically significant (p < 0.05) improvement of 12% to 18% compared with placebo in symptom summary score, daytime asthma symptoms, and albuterol use. No statistically significant differences were observed in pulmonary function. Patient and physician opinions of overall effectiveness favored HFA-cromolyn sodium over placebo (p = 0.01), with no other significant between-treatment differences. No statistically significant differences existed among groups in the incidence of treatment-related adverse events. CONCLUSION: The HFA formulation of cromolyn sodium MDI is a well- tolerated and active alternative treatment for asthma patients aged 12 years and more.

Oxygen-induced changes in protein synthesis and cell proliferation in cultured lung slices.

Elevated fractions of inspired O2 induce significant remodeling of the airways and vasculature of the lung. The present study was undertaken to determine the direct effects of altered levels of O2 on protein synthesis and cell proliferation in lung tissue cultured in vitro. Rat lungs were inflated with low-melt agarose, cut transversely into 1-mm sections, and cultured in a serum-free medium for up to 7 days in the presence of 10, 21, 40, or 70% O2. Tissue structure integrity was maintained as assessed by light and electron microscopy. Fractional synthesis rates (FSR, %protein/day) of soluble protein from cultured lung homogenates demonstrated an O2 concentration-dependent response. Tissue cultured in the presence of 70% O2 exhibited the highest FSR. The FSR of tissue cultured in 21 or 40% O2 did not differ and demonstrated FSR values greater than tissue cultured in 10% O2. Cell proliferation was assessed histologically in parenchymal gas-exchange regions of lung slices cultured in the presence of 5-bromo-2'-deoxyuridine. Labeling indexes for tissue cultured in 21, 40, or 70% indicated an O2-dependent increase in cell proliferation after 3 days in culture followed by a return to baseline levels after 7 days. Tissue cultured in the presence of 10% O2 showed no change in cell proliferation over time. The data indicate a direct influence of O2 on lung cell growth and proliferation. Additionally, these studies show that this in vitro model may be suitable for further understanding of the mechanistic basis involved in proliferative events during lung injury.

Endobronchial nocardiosis.

The presentation of a Nocardia infection is quite variable. We report a case of nocardiosis presenting as endobronchial obstruction with postobstructive pneumonia and atelectasis, in a patient with a low index of suspicion for bronchogenic carcinoma. Our report emphasizes the importance of considering the diagnosis of endobronchial nocardiosis in patients with endobronchial obstruction and a low index of suspicion for carcinoma, as well as those with a high index of suspicion, but with repeatedly negative biopsies.