cardiovascular-agents and Lung-Diseases--Interstitial

Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.

Topics: Blood Vessels; Cardiovascular Agents; Fibrosis; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Inflammation; Kidney Diseases; Lung Diseases, Interstitial; Raynaud Disease; Scleroderma, Systemic; Skin; Transforming Growth Factor beta; Treatment Outcome

Lung injury is an increasing cause of morbidity and mortality in patients treated with cytotoxic and noncytotoxic drugs. Prompt diagnosis is important because early drug-induced lung injury will often regress with the cessation of therapy. Diagnosis requires a high index of suspicion because infection, radiation pneumonitis, and recurrence of the underlying disease can manifest clinically and radiologically in a similar manner. Because the lungs have only a limited number of histopathologic responses to injury, including pulmonary edema/diffuse alveolar damage, NSIP, BOOP, EP, and pulmonary hemorrhage, knowledge of these manifestations and the corresponding radiologic manifestations can often be useful in suggesting a diagnosis of drug-induced lung injury. An understanding of the drugs most commonly associated with lung injury can also facilitate diagnosis.

Topics: Anti-Infective Agents; Antineoplastic Agents; Cardiovascular Agents; Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Hemorrhage; Humans; Lung; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Edema; Pulmonary Eosinophilia; Radiography

Drug-induced pulmonary toxicity is increasing and early diagnosis is important because of the associated morbidity and mortality. Diagnosis is often difficult and is usually based on a history of drug therapy and exclusion of infection, radiation pneumonitis, and recurrence of the underlying disease. Although HRCT findings are frequently nonspecific, diagnosis can be facilitated by an understanding of the most common histopathologic and radiologic manifestations of drug-induced lung injury and knowledge of the drugs usually involved.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Cardiovascular Agents; Cryptogenic Organizing Pneumonia; Female; Hemorrhage; Humans; Lung; Lung Diseases; Lung Diseases, Interstitial; Male; Middle Aged; Pulmonary Eosinophilia; Radiography, Thoracic; Tomography, X-Ray Computed