Diffuse pulmonary calcinosis without calcium metabolism abnormalities in a renal transplant recipient.

Eighteen years after an uneventful renal transplantation, the chest radiograph of an asymptomatic 50 year old man showed diffuse bilateral infiltrations, predominately at the right apex. Computed tomography (CT) scan demonstrated a diffuse alveolar pattern, the alveoli being filled with a very dense material, with some tracheal calcifications. Bronchoalveolar lavage fluid analysis was normal, but bronchial and transbronchial biopsies revealed calcium deposits in the bronchial mucosa and in the alveolar septa. The diagnosis of diffuse pulmonary calcinosis was established, despite normal blood calcium, phosphorus and magnesium levels, based upon computed tomography scan and pathological findings at fibreoptic bronchoscopy, without the need for an open lung biopsy.

Seventy-two hour comparison of methylprednisolone suleptanate and methylprednisolone sodium succinate in patients with acute asthma.

The efficacy and safety of the methylprednisolone prodrugs methylprednisolone suleptanate and methylprednisolone sodium succinate were evaluated in a multicentre, randomised, double-blind, double-dummy parallel study of 88 patients hospitalised with acute asthma. Each study drug was administered as a bolus intravenous injection of 40mg methylprednisolone equivalents every 6 hours for 48 hours. Methylprednisolone 32mg was administered orally 6 hours after the last dose. Pulmonary function, medical events, and clinical laboratory values were assessed at predefined intervals before and during the 72-hour study. The primary response measure of pulmonary function was per cent predicted forced expiratory volume in one second (FEV1) at 48 hours. Secondary response measures were peak expiratory flow rate (PEFR) and FEV1/forced vital capacity (FVC) ratio. Although both drugs demonstrated within-group mean changes from baseline (starting at 6 hours) that were statistically significant for each response, there were no statistically significant differences between the two groups. The mean percent predicted FEV1 at 48 hours and mean per cent change from baseline were 64% and 13% (p < 0.0001) for the methylprednisolone suleptanate group and 67% and 17% (p < 0.0001) for the methylprednisolone sodium succinate group, respectively. The mean PEFR and FEV1/FVC ratio at 48 hours were 5.77 l/s and 73% for the methylprednisolone suleptanate group and 5.78 l/s and 76% for the methylprednisolone sodium succinate group, respectively. There were no clinically or statistically significant between-group differences in any of the safety parameters. In this study, methylprednisolone suleptanate and methylprednisolone sodium succinate have been shown to be therapeutically equivalent in the treatment of patients hospitalized with acute asthma.

Arachidonate 5-lipoxygenase metabolism in human neutrophils from patients with asthma: in vitro effect of nedocromil sodium.

Among the cells which participate in amplification of the local inflammatory reaction in asthma, neutrophils (PMN) are pro-inflammatory cells that can generate inflammatory mediators and arachidonic acid derivatives in particular. In asthmatic patients (AP) with attacks, the capacity of blood PMN to produce 5-lipoxygenase metabolites was investigated and compared to the response in healthy subjects (HS). PMN from 6 AP and from 6 HS were stimulated by calcium ionophore A23187 and arachidonate 5-lipoxygenase metabolites were analyzed by reverse-phase HPLC. LTB4, 6-trans LTB4, omega OH-LTB4 and 5-HETE were identified. In AP, total LTB4 synthesis was enhanced as compared to synthesis with PMN in HS. But the total 5-HETE synthesis by PMN from AP was decreased. Thus, the inflammatory potential of PMN from AP was enhanced in comparison to HS. The anti-inflammatory effect of nedocromil sodium (NS) was studied in the 5-lipoxygenase metabolism of arachidonic acid. NS (10(-4) mol/l) inhibited total LTB4 synthesized by PMN in AP but not in HS. We conclude that NS affects leukotriene synthesis only in cells with enhanced inflammatory potential.

Enhanced arachidonic acid metabolism and human neutrophil migration in asthma.

In stable state asthmatic patients (AP) without any airway obstruction, the capacity of peripheral blood polymorphonuclear neutrophils (PMN) to produce 5-lipoxygenase metabolites and to migrate, was investigated and compared with the response in healthy subjects (HS). After calcium-ionophore A23187 stimulation, PMN from AP and HS produced LTB4, its hydroxylated derivatives: omega-OH-and omega-CO2H-LTB4) (omega-LTB4, i.e 6-trans-LTB4 and 5,6-diHETE isomers, and 5-HETE. We found an increase in LTB4 (+59%), omega-LTB4 (+39%), 6-trans-LTB4 (+128%), and free 5-HETE (+63%) generation of AP as compared with HS. Unstimulated migration was enhanced in AP (122 +/- 27 PMN/10 high power fields (hpf) in AP versus 74 +/- 25 PMN/10 hpf in HS, p less than 0.025) and suggested a greater capacity of PMN from AP to migrate. This was confirmed by the PAF-induced chemotaxis studies which showed, in AP, a greater PAF-sensitivity of PMN (10(-6) M versus 10(-5) M in HS) and a greater chemotaxis response (600 +/- 50 PMN versus 200 +/- 35 PMN in HS). In AP, we compared the capacity of PMN to generate LTB4 and 5-HETE with their capacity to migrate. We found an inverse correlation (r = 0.86, p less than 0.007) of intracellular free 5-HETE with chemotaxis to PAF.

Ambulatory long-term subcutaneous salbutamol infusion in chronic severe asthma.

Although most patients with asthma improve with currently available drugs, there appears to be a subset of patients with asthma resistant to intensive treatment, including large doses of systemic corticosteroids. In 10 patients with asthma difficult to treat, a double-blind, placebo-controlled, crossover study was performed to evaluate whether long-term, continuous subcutaneous infusion of large doses of salbutamol, in addition to steroids, could improve pulmonary function, compared with intermittent nebulization of salbutamol. Four weeks of administration of large doses (greater than 14 mg/day) of beta 2-agonists were well tolerated, elicited a significant decrease of corticosteroid consumption (p less than 0.01), and were associated with an improvement in pulmonary function (p less than 0.01), compared with run in or the placebo administration period. Mean morning and evening peak expiratory flow rates were similar during all periods, and the variability between morning and evening peak expiratory flow rates was only slightly and nonsignificantly reduced during the period when salbutamol was administered subcutaneously. Both nebulized and subcutaneous salbutamol elicited similar metabolic and muscular side effects, but these untoward reactions never caused any patient to stop the treatment. Local infection at the injection site was observed in two of 10 patients with continuous subcutaneous infusion. Tachyphylaxis to beta 2-agonist, as measured by the reversibility of FEV1 to inhaled salbutamol 12 hours after the end of each period, did not occur. In conclusion, large doses of beta 2-agonist administered to patients with severe, chronic, and steroid-dependent asthma were able to improve respiratory function and to decrease corticosteroids requirements.