Enfisema pulmonar por déficit de alfa-1 antitripsina: aspectos fisiopatológicos y de tratamiento / Pulmonary emphysema by alpha-1-antitrypsin deficiency: pathophysiology aspects and treatment

El déficit de alfa-1 antitripsina (a-1 AT), también llamado inhibidor de proteasa, es un defecto genético asociado al desarrollo de enfisema pulmonar precoz y menos frecuentemente a cirrosis hepática. Los fenotipos asociados son PiZZ y PiZNulo, caracterizados por un nivel de a-1 AT plasmático menor de 40 mg/dl. La enfermedad pulmonar se presenta habitualmente antes de los 40 años y su progresón es lenta pero puede ser acelerada marcadamente por el hábito tabáquico. La hipótesis del desbalance elastasa-antielastasa postula que la a-1 AT protege al pulmón del daño elastolítico producido por la elastada del neutrófilo. Su déficit lo dejaría altamente vulnerable a una destrucción progresiva que culmina en el enfisema clínico. Como la terapia de aumentar la producción endógena de a-1 AT o disminuir la elastasa no han tenido éxito, su enfoque actual se ha centrado en aumentar la a-1 AT en forma exógena con infusiones iv mensuales, lo que se está probando en un estudio multicéntrico europeo. La terapia genética se encuentra aún en fase experimental

Inspiratory spirogram in emphysema.

Bronchodilator therapy on inspiratory indices has not been documented so far. Reduction in inspiratory airflow resistance following inhalation of bronchodilator giving the most consistent and significant changes in emphysematous patients has been demonstrated in the present study.

Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response.

A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years.

Comparison of bronchodilatation produced by an anticholinergic (ipratropium bromide), a beta-2 adrenergic (fenoterol) and their combination in patients with chronic obstructive airway disease. An open trial.

Fenoterol hydrobromide (200 micrograms), ipratropium bromide (40 micrograms) and a combination of the two in the same dosage were administered by metered dose inhaler on 3 separate days to 20 patients with chronic bronchitis and emphysema. On each day, baseline forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow rate (PEFR) and mid maximum flow rate (MMFR) were recorded. The values were again recorded after administration of the drug at 15, 30, 45 and 60 minutes. Side effects if any were recorded. There was a significant increase from baseline in FVC and FEV1 with all the three regimens at 15, 30 and 45 minutes. However, the rise in MMFR was significant only with ipratropium bromide and the combination regimen. At 60 minutes, the rise in FVC, FEV1 and MMFR was significant only with the combination regimen. There was no significant change in the PEFR values at any time with any drug. The difference in rise in all the four parameters with the 3 regimens was not statistically significant. No side effects were noted. Thus, a combination fenoterol and ipratropium bromide produced a more prolonged bronchodilatation, and ipratropium bromide perhaps acts both in the major (indicated by rise in FEV1) and small airways (measured by MMFR).