COPD
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Although less well appreciated than pulmonary emphysema, inflammation of the airways is an early and important finding in alpha-1 antitrypsin deficiency (AATD). The spectrum of clinical presentations of airways disease includes cough and wheezing that is frequently diagnosed as asthma. Study of the airways inflammation in sputum or the proximal airways usually reveals neutrophilic inflammation. ⋯ Other phenotypes of varicose and saccular bronchiectasis have been described. Since AAT may impact the course of bacterial, mycobacterial and viral clearance, future studies of the airway microbiota will inform whether airway pathogens are responsible for some pulmonary AATD phenotypes. Whether airways disease improves with AAT augmentation therapy remains unknown.
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Elastases of both the neutrophil and macrophage have been implicated in lung disease initiation and progression. Although it is unlikely that these proteases evolved for the purpose of injuring lung tissue, the elastin-rich connective tissue framework of the lungs appears to be particularly susceptible to the action of elastolytic proteases. Assuming that neutrophil elastase most likely plays a role in the migration of neutrophils toward a site of inflammation and degradation of proteins from invading organisms or other products of the inflammatory response, it is the role of inhibitors of this protease to protect normal tissues from its effects. In alpha-1 antitrypsin deficiency we find an experiment of nature that disrupts this protease-anti-protease balance, resulting in an increased risk of destructive lung disease.
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Clinical research in chronic obstructive pulmonary disease (COPD) has been hampered by the lack of validated blood biomarkers. The ideal COPD biomarker would have the following characteristics: (1) it would be a lung specific protein that could be assayed in blood; (2) it would change with disease severity or during exacerbations; (3) it would be specific for COPD; and would be responsive to change with effective treatments. One such candidate is the lung specific protein surfactant protein D (SP-D). In this review, we discuss the evidence supporting SP-D as a COPD biomarker.
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COPD is defined by airflow limitation that is not fully reversible and is usually progressive. Thus, airflow obstruction (measured as FEV(1)) has traditionally been used as the benchmark defining disease modification with therapy. However, COPD exacerbations and extrapulmonary effects are common and burdensome and generally become more prominent as the disease progresses. ⋯ Smoking cessation, lung volume reduction surgery, inhaled maintenance pharmacotherapy, and pulmonary rehabilitation administered in the post-exacerbation period may reduce mortality in COPD. These improvements over multiple outcome areas and over relatively long durations suggest that disease modification is indeed possible with existing therapies for COPD. Therefore, therapeutic nihilism in COPD is no longer warranted.