Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

Background: Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD), although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT) deficiency (PiZ phenotype) and COPD. Methods: Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year. Results: The patients (n = 23) had a mean age of 52.5 years, forced expiratory volume in one second (FEV1) of 1.2 L (38.4% predicted), corrected gas transfer (KCO) of 0.90 mmol/min/kPa/L (59.7% predicted), and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated) were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = -0.432; P = 0.022). Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available) correlated negatively with baseline 15th percentile lung density (r = -0.361; P = 0.003), and increased the longer treatment was delayed (r = 0.503; P, 0.001). Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = -0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036,,0.001, and,0.001, respectively). Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = -0.647; P = 0.007). Conclusion: In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment delay adversely affected exacerbation length, and lung density was the best independent predictor of delay in starting treatment. Keywords: alpha-1 antitrypsin deficiency, antibiotic, exacerbation, gas transfer, lung density, lung function