Current Respiratory Medicine Reviews - Volume 5, Issue 2, 2009

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The concentration of airborne particulate matters (PM) is related to daily hospital admissions for several pulmonary disorders such as bronchial asthma, acute and chronic bronchiolitis, and pneumonia. Especially, PM with a mass median aerodynamic diameter < or 2.5 μm (PM2.5) is recognized to be more closely associated with respiratory effects and subsequent mortality than that of mass median aerodynamic diameter < or 10 μm (PM10). However, there has been insufficient experimental evidence and their underlying mechanisms to support these epidemiological investigations. In this review, we introduce the adverse effects of PM, particularly, diesel exhaust particles, the main constituents of PM, on several pulmonary diseases, showing our in vivo evidence. Further, we also focus on the effects of nanoparticles, particles less than 100 nm in mass median aerodynamic diameter, on respiratory tract and disorders.

COPD is a condition characterized by progressive airflow obstruction which is rather insensible to bronchodilators. The pathogenetic mechanisms of this disorder are multifaceted, encompassing pulmonary inflammation, small airway remodelling, emphysema and mucous hypersecretion. As our comprehension of the heterogeneous pathology of the disease has improved it has been recognized that the ongoing inflammatory process in COPD is correlated with the relentlessness of this condition. Therefore, the scientific interest has been directed in the development of new anti-inflammatory drugs targeting pulmonary inflammation. In this survey, we will try to evaluate current treatment options and the potential and efficacy of new treatment modalities.

Joshanda, a polyherbal Unani (Greco-arab) formulation is extensively used in the treatment of upper and lower respiratory catarrh. After the renewed attention and interest in the use of traditional medicines at the global level, Joshanda is extensively being used for the treatment of URC (Upper Respiratory Catarrh), particularly in the chronic cases. This polyherbal mixture contains a variety of expectorant, anticatarrhal and respiratory demulcent herbs that help in relieving the debilitating cough. The key to success of this highly effective phytotherapy lies in the use of a combination of antitussive agents that act by different modes e.g. reflex expectorants, central expectorants, parasympathetomimetics, stimulants of secretory cells and secretomotorics. Although a large volume of work has been reported on its individual constituents, there is hardly any literature available on Joshanda, as a formulation. Contrary to the common belief that the phytoconstituents are always safe, the individual constituents are known to cause long term toxicity and show some drug interactions. As a result, the formulation may show certain adverse effects on very long term use. The review presents the rationale behind the use of various drugs used in this polyherbal combination. It also gives a detailed account of the chemistry and pharmacology of the various active phytoconstituents. The side effects and drug interactions related to the constituents of the formulation are also discussed.

Despite advances in antimicrobial therapy and supportive measures, mortality in patients with severe community- acquired pneumonia admitted to the intensive care unit remains high, especially in case of development of sepsis with its complications. Systemic inflammation is a major feature of severe community-acquired pneumonia worsening to sepsis. This uncontrolled inflammation is sustained by genetic mechanisms throughout an exaggerated activation of the nuclear factor NF-κB. Glucocorticoids inhibit the activity of NF-κB intracellularly. On the base of this concept, the data emerged from scientific literature and from a recent randomized trial on patients with severe community acquired pneumonia support the hypothesis that prolonged infusion of low doses of hydrocortisone may accelerate the resolution of the pneumonia and prevent the development of severe complications due to sepsis. Moreover, this therapeutic approach seems to be associated with a significant reduction in duration of mechanical ventilation, length of hospital stay and long-term mortality.

Environmental tobacco smoke (ETS) exposure has been associated with adverse health outcomes in all stages of life. Embryogenesis is a particularly important period to study because exposures during this period can alter proper growth and development of all organs. ETS exposure to the developing fetus has been associated with low birth weight infants, premature births and sudden infant death syndrome. In addition, prenatal ETS exposure has been identified as a significant risk factor for the development of asthma in a number of epidemiologic studies. This review surveys the current literature available linking in utero ETS with the development of asthma, explores the role of nicotine as a possible causative agent involved in the pathogenesis of these findings, and examines the literature linking in utero ETS exposure with broader effects on airway physiology and response.

Electrical Impedance Tomography is a non invasive lung function monitoring with the possibility of regional lung function studies concerning regional ventilation, regional lung perfusion and regional lung mechanics. This review describes the technique of Electrical Impedance Tomography, its possibility, limitations, and use in research and its possible use in clinical routine.

Alveolar capillary dysplasia (ACD) is a recently recognized lethal lung malformation. ACD is a rare congenital disorder of pulmonary vascular development associated with unremitting hypoxemia and respiratory failure. This paper reviews the incidence, pathophysiology and histopathology, clinical manifestations, diagnosis, and treatment of affected newborns and proposes an algorithmic approach to management of infants who present with unremitting persistent pulmonary hypertension of the newborn.

Pulmonary arterial hypertension (PAH) is characterized by progressive obliteration of the small pulmonary vasculature leading to permanently increased vascular resistance and elevated pulmonary artery pressures over 25 mmHg at rest and 30 mmHg during exercise. Elevated pressures in the pulmonary circulation result in right heart failure and premature death. Besides idiopathic PAH, it can also occur in a variety of other conditions such as connective tissue diseases. Mainly patients suffering from systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis may be affected. In these patients, PAH may occur in association with left heart disease, interstitial fibrosis or as a result of an isolated pulmonary arteriopathy. The mechanisms leading to PAH remain unknown even if a pathophysiological model includes vasoconstrictor/vasodilator imbalance, thrombogenic factors, misguided angiogenesis and pro-inflammatory factors. Symptoms and clinical presentation are very similar to idiopathic PAH but mortality was confirmed to be higher. A 2-D echoDoppler examination is considered as the first-line diagnostic tool, however the results should be confirmed by right heart catheterization. Unfortunately, despite recent major improvements in PAH treatment, no current therapy can yet cure this devastating condition. Intravenous epoprostenol therapy has been proved to improve exercise capacity and symptoms in patients with systemic sclerosis. Also the endothelin receptor antagonists (bosentan and sitaxentan), the phosphodyesterase-type-5 inhibitor (sildenafil) and subcutaneous treprostinil have shown favourable results. Despite recent advances in treatment, PAH remains essentially untreatable even if pharmacological trials seem to slow down progression of the disease improving symptoms and quality of life of these patients.

Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening pulmonary manifestation that has been associated with various diseases. It is a medical emergency that requires prompt diagnosis and aggressive treatment. The clinical manifestations consist of hemoptysis, hypoxia, a drop in the hemoglobin level and new pulmonary infiltrates on chest X-ray. Infrequently, Systemic lupus erythematosus (SLE) and Antiphospholipid syndrome (APS) could be complicated by this severe pulmonary manifestation. The most common histologic lesion in SLE and Antiphospholipid Syndrome is pulmonary capillaritis. Corticosteroids with or without immunosuppressive agents such as cyclophosphamide are the mainstay of the therapy. Plasmapheresis, intravenous immunoglobulin or the newer biologic agents would be considered if there is a persistent lack of clinical response.