Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results

Inhaled corticosteroids (ICS) are important in reducing exacerbation frequency associated with chronic obstructive pulmonary disease (COPD). However, little is known about the risk of associated infections. In a post hoc analysis of the TOwards a Revolution in COPD Health (TORCH) study, we analysed and identified potential risk factors for adverse event reports of pneumonia in this randomised, double-blind trial comparing twice-daily inhaled salmeterol (SAL) 50 μg, fluticasone propionate (FP) 500 μg, and the combination (SFC) with placebo in 6,184 patients with moderate-to-severe COPD over 3 yrs. Despite a higher withdrawal rate in the placebo arm, after adjusting for time on treatment, a greater rate of pneumonia was reported in the FP and SFC treatment arms (84 and 88 per 1,000 treatment-yrs, respectively) compared with SAL and placebo (52 and 52 per 1,000 treatment-yrs, respectively). Risk factors for pneumonia were age ≥55 yrs, forced expiratory volume in 1 s <50% predicted, COPD exacerbations in the year prior to the study, worse Medical Research Council dyspnoea scores and body mass index <25 kg·m−2. No increase in pneumonia deaths with SFC was observed; this could not be concluded for FP. Despite the benefits of ICS-containing regimens in COPD management, healthcare providers should remain vigilant regarding the possible development of pneumonia as a complication in COPD patients receiving such therapies.

[1]  A. Anzueto,et al.  Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. , 2008, Respiratory medicine.

[2]  A. Anzueto,et al.  Effect of fluticasone propionate/salmeterol (250/50 g) or salmeterol (50 g) on COPD exacerbations , 2008 .

[3]  T. Seemungal,et al.  The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. , 2008, American journal of respiratory and critical care medicine.

[4]  A. Gonzalez,et al.  Inhaled corticosteroid use in chronic obstructive pulmonary disease and the risk of hospitalization for pneumonia. , 2007, American journal of respiratory and critical care medicine.

[5]  R. Moots,et al.  Haemophilus influenzae induces neutrophil necrosis: a role in chronic obstructive pulmonary disease? , 2007, American journal of respiratory cell and molecular biology.

[6]  R. Djukanović,et al.  Impaired neutrophil chemotaxis in chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[7]  Bartolome Celli,et al.  Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. , 2007, The New England journal of medicine.

[8]  Robert A Wise,et al.  Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee , 2007, Thorax.

[9]  J. Maurer Trends in Hospitalizations for Pneumonia Among Persons Aged 65 Years or Older in the United States, 1988–2002Fry AM, Shay DK, Holman RC, et al (Centers for Disease Control and Prevention, Atlanta, Ga) JAMA 294:2712–2719, 2005§ , 2007 .

[10]  A. Anzueto,et al.  COPD is associated with increased mortality in patients with community-acquired pneumonia , 2006, European Respiratory Journal.

[11]  J. Rello,et al.  Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia , 2006, European Respiratory Journal.

[12]  S. Johnston,et al.  Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. , 2006, American journal of respiratory and critical care medicine.

[13]  S. Sethi,et al.  Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

[14]  I. Pavord,et al.  Antiinflammatory effects of salmeterol/fluticasone propionate in chronic obstructive lung disease. , 2006, American journal of respiratory and critical care medicine.

[15]  R. Holman,et al.  Trends in hospitalizations for pneumonia among persons aged 65 years or older in the United States, 1988-2002. , 2005, JAMA.

[16]  Fernando Holguin,et al.  Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. , 2005, Chest.

[17]  P. Jeffery Anti-inflammatory effects of inhaled corticosteroids in chronic obstructive pulmonary disease: similarities and differences to asthma , 2005, Expert opinion on investigational drugs.

[18]  C. Jenkins,et al.  The TORCH (TOwards a Revolution in COPD Health) survival study protocol , 2004, European Respiratory Journal.

[19]  P. Calverley,et al.  Maintenance therapy with budesonide and formoterol in chronicobstructive pulmonary disease , 2003, European Respiratory Journal.

[20]  S. Hodge,et al.  Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells , 2003, Immunology and cell biology.

[21]  J. Wedzicha,et al.  Airway bacterial load and FEV1 decline in patients with chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[22]  R. Pauwels,et al.  Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial , 2003, The Lancet.

[23]  M. Leinonen,et al.  Pneumonic vs Nonpneumonic Acute Exacerbations of COPD , 2002, Chest.

[24]  J. Izquierdo,et al.  Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical (inmunoferón). , 2001, American journal of respiratory and critical care medicine.

[25]  C L Bartlett,et al.  Risk factors for community-acquired pneumonia diagnosed upon hospital admission. British Thoracic Society Pneumonia Study Group. , 2000, Respiratory medicine.

[26]  A. Ilgazlı,et al.  Inhaled Corticosteroids May Reduce Neutrophilic Inflammation in Patients with Stable Chronic Obstructive Pulmonary Disease , 2000, Respiration.

[27]  H. V. van Saene,et al.  Oropharyngeal gram-negative bacillary carriage in chronic obstructive pulmonary disease: relation to severity of disease. , 1999, Respiratory medicine.

[28]  C. Agustí,et al.  Bacterial colonization of distal airways in healthy subjects and chronic lung disease: a bronchoscopic study. , 1997, The European respiratory journal.

[29]  D. McDonald,et al.  Salmeterol reduces early- and late-phase plasma leakage and leukocyte adhesion in rat airways. , 1997, American journal of respiratory and critical care medicine.

[30]  P. Henricks,et al.  Increased cAMP levels in stimulated neutrophils inhibit their adhesion to human bronchial epithelial cells. , 1997, The American journal of physiology.

[31]  F. Dallegri,et al.  Inhibitory effect of salmeterol on the respiratory burst of adherent human neutrophils , 1996, Clinical and experimental immunology.

[32]  S. Abe,et al.  Decreased contents of surfactant proteins A and D in BAL fluids of healthy smokers. , 1996, Chest.

[33]  J. Vestbo,et al.  Risk factors for death and hospitalization from pneumonia. A prospective study of a general population. , 1995, The European respiratory journal.

[34]  J. Ruiz,et al.  Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. , 1995, American journal of respiratory and critical care medicine.

[35]  R. Stockley,et al.  Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro. , 1994, Thorax.

[36]  T. Murphy,et al.  Bacterial infection in chronic obstructive pulmonary disease. , 1992, The American review of respiratory disease.

[37]  S. Schwartz,et al.  Effects of alcohol and nicotine on cytotoxic functions of human lymphocytes. , 1990, Clinical immunology and immunopathology.