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Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease.

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Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2013 Nov 1;188(9):1052-7

Authors: Miravitlles M, Anzueto A

Abstract
Prevention and effective treatment of exacerbations are major objectives in the management of patients with chronic obstructive pulmonary disease (COPD). Antibiotics are mainstay treatment for patients with severe COPD with an acute exacerbation that includes increased sputum purulence and worsening shortness of breath. Although such treatment is associated with clinical benefit, treatment failure and relapse rates may be high, particularly in cases of inadequate antibiotic therapy through incomplete resolution of the initial exacerbation and persistent bacterial infection. These aspects have led to recommendations for a stratified approach to antibiotic therapy based on patient characteristics associated with increased risk factors for failure. Patients at greatest risk for poor outcome (i.e., those with severe COPD) are likely to derive greatest benefit from early treatment with antibiotics. Long-term or intermittent antibiotic treatment has been shown to prevent COPD exacerbations and hospitalizations. These effects may be achieved by reducing bacterial load in the airways in stable state and/or bronchial inflammation. Although systemic antibiotics are likely to remain the core treatment for patients with moderate to severe exacerbated COPD, inhaled antibiotics may represent a more optimal approach for the treatment and prevention of COPD exacerbations in the future. Regardless of the route of administration, further studies are required to evaluate the potential long-term adverse events of antibiotics and the development of bacterial resistance.

PMID: 23924286 [PubMed - indexed for MEDLINE]

Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease.

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Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2013 Nov 1;188(9):1091-9

Authors: Patel AR, Kowlessar BS, Donaldson GC, Mackay AJ, Singh R, George SN, Garcha DS, Wedzicha JA, Hurst JR

Abstract
RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.
OBJECTIVES: To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.
METHODS: We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.
MEASUREMENTS AND MAIN RESULTS: COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).
CONCLUSIONS: Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

PMID: 24033321 [PubMed - indexed for MEDLINE]

Statin exposure is associated with decreased asthma-related emergency department visits and oral corticosteroid use.

Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects.

OBJECTIVES: To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort.

METHODS: Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non-statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression.

MEASUREMENTS AND MAIN RESULTS: Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53-0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04). There were no differences in asthma-related hospitalizations (OR, 0.91; 95% CI, 0.66-1.24; P = 0.52).

CONCLUSIONS: Among statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings.

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials.

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Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities.

METHODS: The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF).

RESULTS: A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed.

CONCLUSION: Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.

Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review.

The connective tissue diseases (CTDs) are a group of systemic disorders characterized by autoimmunity and autoimmune-mediated organ damage. The lung is a frequent target and all components of the respiratory system are at risk.

Interstitial lung disease (ILD) represents a broad group of diffuse parenchymal lung injury patterns characterized by varying degrees of inflammation and fibrosis, is a common manifestation of CTD particularly common in systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis, and is a leading cause of significant morbidity and mortality. The lung injury patterns of CTD-associated ILD (CTD-ILD) mirror those of idiopathic interstitial pneumonia and may arise at any time during the course of the CTD or may be the first manifestation of CTD. Patients with CTD that present with respiratory failure often present significant diagnostic dilemmas.

Thorough and comprehensive assessments to exclude respiratory *infection, acute interstitial pneumonia, medication toxicity, pulmonary embolism, cardiac dysfunction, and diffuse alveolar hemorrhage are the fundamental components for the evaluation of such patients. Furthermore, patients with CTD are also at risk of acute exacerbations of underlying ILD. Acute exacerbations are manifested by subacute respiratory deterioration with worsening hypoxemia in the setting of new radiographic abnormalities.

The prognosis of patients with CTD having respiratory failure is often quite poor, highlighting the need for prompt and thorough clinical assessments to determine the underlying etiology and implementation of appropriate therapeutic strategies.

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