Respiration; international review of thoracic diseases
-
Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. ⋯ These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections.
-
More than 50 years ago, the observation that absence of the α1 band from protein electrophoresis is associated with severe emphysema established the link between α1-antitrypsin deficiency (AATD) and lung damage. From this discovery, the classic paradigm of protease/antiprotease imbalance was derived, linking lung destruction in patients with AATD to the unopposed effect of proteases. ⋯ From this perspective, we will consider recent evidence, based on epidemiological, clinical and immunopathological studies, suggesting that it is time to move on from the original protease/antiprotease paradigm toward a more complex view of the condition, which embraces its immunomodulating functions. Of importance, the potent immunoregulatory, tolerogenic role of AAT may support its therapeutic use in a number of diseases other than AATD, particularly in immune-related disorders.
-
Review Comparative Study
Interstitial lung disease evaluation: detecting connective tissue disease.
Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD) and is often associated with significant morbidity and mortality. The evaluation of ILD in patients with CTD is complex because of the heterogeneity of the CTD spectrum, the various patterns and degrees of severity of ILD encountered, and because ILD can be identified at any point in time in these patients. ⋯ Determining whether ILD is associated with a preexisting CTD requires the exclusion of alternative etiologies, and thorough assessments of the clinical features of both the CTD and ILD. The detection of occult CTD in patients with presumed idiopathic interstitial pneumonia requires careful integration of clinical, serologic, and thoracic imaging and histopathologic features.
-
The clinical syndrome of acute lung injury (ALI) occurs as a result of an initial acute systemic inflammatory response. This can be consequent to a plethora of insults, either direct to the lung or indirect. The insult results in increased epithelial permeability, leading to alveolar flooding with a protein-rich oedema fluid. ⋯ In addition, there is a significant burden of morbidity in survivors. There are currently no disease-modifying therapies available, and the most effective advances in caring for these patients have been in changes to ventilator strategy as a result of the ARDS network studies nearly 15 years ago. Here, we will give an overview of more recent advances in the understanding of the cellular biology of ALI and highlight areas that may prove fertile for future disease-modifying therapies.
-
Due to the high etiological diversity and the potential for malignancy, pulmonary nodules represent a clinical challenge, becoming increasingly frequent as the number of CT examinations rises. The topic gains even more importance as clear evidence for the effectiveness of CT screening was provided by the National Lung Screening Trial (NLST). Yet, the results were tempered by the high false-positive rate and the requirement of performing further diagnostic procedures. The management of those detected solitary pulmonary nodules is currently based on the individuals' risk of developing lung cancer, the pulmonary nodule characteristics and the capability of diagnostic and therapeutic approaches.