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

Kesavaperumal Vijayasaratha, Robert A Stockley, Kesavaperumal Vijayasaratha, Robert A Stockley

Abstract

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 (FEV(1)) 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 FEV(1), FEV(1)/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.

Trial registration: ClinicalTrials.gov NCT00263887.

Keywords: alpha-1 antitrypsin deficiency; antibiotic; exacerbation; gas transfer; lung density; lung function.

Figures

Figure 1
Figure 1
Diagrammatic representation of exacerbation length and components.
Figure 2
Figure 2
Correlation between KCO (% predicted) and frequency of 164 treated exacerbations in 21 patients. Notes: Each point is the average number of treated episodes/year for each patient. The correlation coefficient (r) and significance of the relationship are shown. Abbreviation: KCO, corrected gas transfer.
Figure 3
Figure 3
Relationship between delay in starting antibiotic treatment and length of exacerbation. Notes: Each point represents an individual antibiotic-only treated (no systemic steroid) episode (n = 49 in 15 patients). The correlation coefficient (r) and significance are shown.
Figure 4
Figure 4
Association between treatment delay and baseline PD15. Notes: Each point represents the average delay for each of the 15 patients whose antibiotic-treated episodes were studied in detail. The correlation coefficient (r) is shown, together with the significance of the relationship. Abbreviation: PD15, 15th percentile lung density.
Figure 5
Figure 5
Relationship between gas transfer and resolution of exacerbation after treatment start. Notes: Each point represents the average resolution time for each of the 15 patients who experienced and documented antibiotic-treated episodes. The value for the coefficient (r) and the P-value are again shown. Abbreviation: KCO, corrected gas transfer.

References

    1. Kendrick S. Emergency admissions: what is driving the increase? Health Serv J. 1995;105:26–28.
    1. Mushlin AI, Black ER, Connolly CA, Buonaccorso KM, Eberly SW. The necessary length of hospital stays for chronic pulmonary disease. JAMA. 1991;266:80–83.
    1. Seneff MG, Wagner DP, Wagner RP, Zimmerman JE, Knaus WA. Hospital and one year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA. 1995;274:1852–1857.
    1. Connors AF, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. Am J Respir Crit Care Med. 1996;154:959–967.
    1. Hurd S. The impact of COPD on lung health worldwide: epidemiology and incidence. Chest. 2000;117:1S–4S.
    1. Almagro P, Calbo E, de Echaguen Ochoa, et al. Mortality after hospitalisation for COPD. Chest. 2002;121:1441–1448.
    1. Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality related factors after hospitalisation for acute exacerbations of COPD. Chest. 2003;124:459–467.
    1. A Statistics Report from the British Thoracic Society. The Burden of Lung Disease. 2nd ed. 2006. [Accessed October 24, 2012]. Available from: .
    1. Dowson LJ, Guest PJ, Stockley RA. Longitudinal changes in physiological, radiological and health status measurements in alpha (1)-antitrypsin deficiency and factors associated with decline. Am J Respir Crit Care Med. 2001;164:1805–1809.
    1. Needham M, Stockley RA. Exacerbations in alpha 1 antitrypsin deficiency. Eur Respir J. 2005;25:992–1000.
    1. Donaldson GC, Seemungal TAR, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847–852.
    1. Seemungal TAR, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:1418–1422.
    1. Doll H, Grey-Amante P, Duprat-Lomon I, et al. Quality of life in acute exacerbation of chronic bronchitis: results from a German population study. Respir Med. 2002;96:39–51.
    1. Pauwels RA, Lofdahl CG, Laitinen LA, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med. 1999;340:1948–1953.
    1. Paggiaro PL, Dahle R, Bakran I, Frith L, Hollingworth K, Efthimiou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. Lancet. 1998;351:773–780.
    1. Mahler DA, Donohue JF, Barbee RA, et al. Efficacy of salmeterol xinafoate in the treatment of COPD. Chest. 1999;115:957–965.
    1. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002;19:217–224.
    1. Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate vs salmeterol on exacerbations in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:144–149.
    1. Vincken W, van Noord JA, Greefhorst AP, et al. Improved health outcomes in patients with COPD during 1 year’s treatment with tiotropium. Eur Respir J. 2002;19:209–216.
    1. Aaron SD, Sandemheen LK, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol or fluticasone/salmeterol for treatment of chronic obstructive pulmonary disease. Ann Intern Med. 2007;146:545–555.
    1. Niewoehner DE, Rice K, Cote C, et al. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005;143:317–326.
    1. Brusasco V, Hodder R, Miravitlles M, Korducki L, Towse L, Kesten S. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax. 2003;58:399–404.
    1. Celli B, Calverley PM, Anderson JA, et al. The towards a revolution in COPD health (TORCH) study: fluticasone propionate/salmeterol reduces the rate of exacerbations over 3 years. Chest. 2006;130:177s.
    1. Chong J, Karner C, Poole P. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9:CD009157.
    1. Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012;9:CD006829.
    1. Stockley RA, O’Brien C, Pye A, et al. Relationship of sputum color to nature and outpatient management of acute exacerbations of COPD. Chest. 2000;117:1638–1645.
    1. Bhowmik A, Seemungal TA, Sapsford RJ, Wedzich JA. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 2000;55:114–120.
    1. Patel IS, Seemungal TA, Wilks M, Lloyd-Owen SJ, Donaldson GC, Wedzicha JA. Relationship between bacterial colonization and the frequency, character and severity of COPD exacerbations. Thorax. 2002;57:759–764.
    1. Seemungal TA, Harper-Owen R, Bhowmik A, et al. Respiratory viruses, symptoms and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;164:1618–1623.
    1. McElvaney NG, Stoller JK, Buist AS, et al. Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute Registry of alpha 1-antitrypsin deficiency. Alpha 1-Antitrypsin Deficiency Registry Study Group. Chest. 1997;111:394–403.
    1. Eden E, Hammel J, Rouhani FN, et al. Asthma features in severe alpha1-antitrypsin deficiency: experience of the National Heart, Lung, and Blood Institute Registry. Chest. 2003;123:765–771.
    1. Eriksson S. Pulmonary emphysema and alpha-1-antitrypsin deficiency. Acta Med Scand. 1963;175:197–205.
    1. Wilson JS, Galvin JR. Normal diffusing capacity in patients with Pi ZZ alpha(1)-antitrypsin deficiency, severe airflow obstruction, and significant radiographic emphysema. Chest. 2000;118:867–871.
    1. Fabbri LM, Luppi F, Beghe B, Rabe KF. Update in chronic obstructive pulmonary disease 2005. Am J Respir Crit Care Med. 2006;173:1056–1065.
    1. Anthonisen NR, Manfreda J, Warren CP, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106:196–204.
    1. Rodriguez-Rosin R. Toward a consensus definition for COPD exacerbations. Chest. 2000;117:398S–401S.
    1. Vijayasaratha K, Stockley RA. Reported and unreported exacerbations of COPD – analysis by diary cards. Chest. 2008;133:34–41.
    1. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK. Randomised double blind placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ. 2000;320:1297–1303.
    1. Langsetmo L, Platt RW, Ernst P, Bourbeau J. Underreporting exacerbation of chronic obstructive pulmonary disease in a longitudinal cohort. Am J Respir Crit Care Med. 2008;177:396–401.
    1. Ball P, Harris JM, Lowson D, Tilltoson G, Wilson R. Acute infective exacerbations of chronic bronchitis. QJM. 1995;88:61–68.
    1. Hill AT, Campbell EJ, Bayley DL, Hill SL, Stockley RA. Evidence for excessive bronchial inflammation during an acute exacerbation of chronic obstructive pulmonary disease in patients with alpha(1)-antitrypsin deficiency (Pi Z) Am J Respir Crit Care Med. 1999;160:1968–1975.
    1. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med. 1998;158:49–59.
    1. Lieberman J. Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting data. Chest. 2000;118:1480–1485.
    1. Wilkinson TMA, Donaldson GC, Hurst JR, et al. Early therapy improves outcomes of exacerbations of COPD. Am J Respir Crit Care Med. 2004;169:1298–1304.
    1. Wedzicha JA, Donaldson GC. Exacerbations of chronic obstructive pulmonary disease. Respir Care. 2003;48:1204–1213.
    1. Parr DG, Stoel BC, Stolk J, Stockley RA. Validation of computed tomographic lung densitometry for monitoring emphysema in α1-antitrypsin deficiency. Thorax. 2006;61:485–490.
    1. Parr DG, Stoel DC, Stolk J, Stockley RA. Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment. Am J Respir Crit Care Med. 2004;170:1172–1178.
    1. Parr DG, Sevenoaks M, Deng C, Stockley RA. Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; methodological advances. Respir Res. 2008;9:21.
    1. Donaldson GC, Seemingul TAR, Patel IS, et al. Longitudinal changes in the nature, severity and frequency of COPD exacerbations. Eur Respir J. 2003;22:931–936.
    1. Garcia-Aymerich J, Monsó E, Marrades RM, et al. Risk factors for hospitalization for a chronic obstructive pulmonary disease exacerbation. EFRAM study. Am J Respir Crit Care Med. 2001;164:1002–1007.
    1. Bourbeau J, Julien M, Mattais F, et al. Reduction of hospital utilisation in patients with COPD: a disease specific self management intervention. Arch Intern Med. 2003;163:585–591.
    1. Gadoury MA, Schwartzman K, Rouleau M, et al. Self-management reduces both short and long term hospitalisation in COPD. Eur Resp J. 2005;26:853–857.
    1. Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:1608–1613.
    1. Stolk J, Putter H, Bakker EM, et al. Progression parameters for emphysema: a clinical investigation. Respir Med. 2007;101:1924–1930.
    1. Stolk J, Ng WH, Bakker EM, et al. Correlation between annual change in health status and computer tomography derived lung density in subjects with α1-antitrypsin deficiency. Thorax. 2003;58:1027–1030.
    1. Dawkins PA, Dowson LJ, Guest PJ, Stockley RA. Predictors of mortality in alpha 1 antitrypsin deficiency. Thorax. 2003;58:1020–1026.
    1. Dirksen A, Piitulainen E, Parr DG, et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha-1-antitrypsin deficiency. Eur Respir J. 2009;33:1345–1353.

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