The American review of respiratory disease
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Am. Rev. Respir. Dis. · Nov 1991
Comparative StudyGlucocorticoid resistance in chronic asthma. Peripheral blood T lymphocyte activation and comparison of the T lymphocyte inhibitory effects of glucocorticoids and cyclosporin A.
A total of 37 chronic severe asthmatic patients with documented reversible airways obstruction were classified as glucocorticoid sensitive or resistant according to changes in the FEV1 following a course of oral prednisolone. The phenotype and expression of activation molecules on peripheral blood T lymphocytes from these patients just before the course of prednisolone were studied using flow cytometry. The resistant patients had significantly elevated percentages of T lymphocytes expressing the activation molecules IL-2R and HLA-DR compared to the sensitive patients. ⋯ Inhibition of elaboration of interleukin-2 and interferon-gamma by mitogen-stimulated T lymphocytes from sensitive and resistant asthmatic patients was also studied. Dexamethasone (10(-7) mol/L) significantly inhibited the production of interleukin-2 and interferon-gamma by proliferating T lymphocytes isolated from the glucocorticoid-sensitive but not the resistant chronic asthmatic patients. Cyclosporin A (500 ng/ml) inhibited the elaboration of both lymphokines by T lymphocytes derived from both patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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Am. Rev. Respir. Dis. · Oct 1991
Clinical usefulness of n-of-1 randomized controlled trials in patients with nonreversible chronic airflow limitation.
To determine if n-of-1 randomized controlled trials (n-of-1 RCT) are useful in the care of patients with nonreversible chronic airflow limitation (CAL). Individual trials had a double-blind, randomized, multiple crossover design. Patients with CAL were recruited from several respirology practices. ⋯ After 8 n-of-1 RCT (44% of all completed, or 31% of all trials) clinicians decided to stop the drug, which would otherwise have been continued indefinitely. In all 17 of the clinically definite n-of-1 RCT, the management decision that followed the trial was still being adhered to 40 months (on average) after completion of the trial. The results support the feasibility and usefulness of n-of-1 RCT in respirology practice.
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Am. Rev. Respir. Dis. · Sep 1991
Effects of positive end-expiratory pressure on alveolar recruitment and gas exchange in patients with the adult respiratory distress syndrome.
The effects of different levels of positive end-expiratory pressure (PEEP) (zero to 15 cm H2O) on the static inflation volume-pressure (V-P) curve of the respiratory system and on gas exchange were studied in eight patients with the adult respiratory distress syndrome (ARDS). Alveolar recruitment with PEEP was quantified in terms of recruited volume, i.e., as difference in lung volume between PEEP and zero end-expiratory pressure (ZEEP) for the same static inflation pressure (20 cm H2O) from the V-P curves obtained at the different PEEP levels. ⋯ The results suggest that: (1) in some patients with ARDS the V-P curves determined on ZEEP exhibit an upward concavity reflecting progressive alveolar recruitment with increasing inflation volume, and PEEP results in alveolar recruitment (range of recruited volume at 15 cm H2O of PEEP: 0.11 to 0.36 L); (2) in other patients with ARDS the V-P curves on ZEEP are characterized by an upward convexity, and PEEP results in a volume displacement along this curve without alveolar recruitment and with enhanced risk of barotrauma; (3) the PEEP-induced increase in arterial oxygenation is significantly correlated to the recruited volume but not to the changes in static compliance. The shape of the static inflation V-P curves on ZEEP allows the prediction of alveolar recruitment with PEEP.
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Am. Rev. Respir. Dis. · Sep 1991
Comparative StudyHuman neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Comparison with interstitial lung disease and evaluation of the effect of intravenously administered antibiotic therapy.
In cystic fibrosis (CF), extracellular lung matrix is progressively damaged, neutrophils invade the air spaces, and activated neutrophils may release large amounts of neutrophil elastase (NE). Although alpha 1-antiprotease (alpha 1-AP) binds and inactivates NE and is the major antielastase of the lower respiratory tract, antielastase defenses may be overwhelmed in CF, leading to progressive lung damage. To determine whether the ability of alpha 1-AP to neutralize NE is impaired in CF, we compared NE activity in bronchoalveolar lavage (BAL) fluid and human neutrophil elastase/alpha 1-antiprotease (NE/alpha 1-AP) complex in both BAL fluid and peripheral blood serum from patients with CF, normal volunteers, and patients with interstitial lung disease. ⋯ Although in interstitial lung disease there was a significant correlation between increased NE/alpha 1-AP complex in BAL or peripheral blood and the degree of neutrophil influx, NE/alpha 1-AP complex was disproportionately low in CF BAL compared with significantly elevated values in serum. These data suggest that in CF, alpha 1-AP-mediated defense against free NE in the lower respiratory tract is significantly impaired, and high levels of uncomplexed, enzymatically active, NE are present in CF respiratory secretions. To determine whether intravenously administered antipseudomonal antibiotic therapy for exacerbations of CF lung disease diminished the amount of free NE in respiratory secretions, we used BAL to investigate the effect of such therapy on neutrophils and NE in patients with CF colonized with pseudomonads.(ABSTRACT TRUNCATED AT 250 WORDS)
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Am. Rev. Respir. Dis. · Sep 1991
Moment analysis of a multibreath nitrogen washout based on an alveolar gas dilution number.
A common method for analyzing a multibreath nitrogen washout (MBNW) is to perform moment analysis and derive the mean dilution number (MDN). A homogeneously mixed alveolar space with zero series dead space (VD = 0) will always result in a MDN = 1, regardless of breathing pattern. A higher MDN implies more inhomogeneity. ⋯ Compared with the MDN, the AMDN showed a significantly wider separation between clinical groups. Also, the AMDN demonstrated an increased variability within both sick groups versus a decrease in the healthy group. We conclude that the AMDN is superior to the MDN because of its decreased sensitivity to breathing pattern but increased sensitivity to degree of disease.