Current Respiratory Medicine Reviews - Volume 5, Issue 3, 2009

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Frequency and type of respiratory manifestations differ among individual rheumatic diseases in childhood as well as among children and adults. It is important to recognise respiratory complications of established diseases like juvenile systemic lupus erythematosus or dermatomyositis early enough to prevent serious disease outcomes. Nevertheless, it is of the same importance to reveal unusual characteristics of respiratory symptoms which rheumatic disease may present with, like in Wegener's granulomatosis. Therefore high degree of suspicion and good access to specialised paediatric care including paediatric rheumatology and intensive care units are often of vital importance. In this review respiratory symptoms are summarised firstly by anatomical location of affected area and secondly by individual rheumatic diseases. Where applicable, differences between paediatric and adult disease are shown and main diagnostic and therapeutic principles overviewed. Disease spectrum covers juvenile idiopathic arthritis, juvenile systemic lupus erythematosus and dermatomyositis, systemic scleroderma and primary systemic vasculitides.

The pathobiology of CF lung disease has yet to be fully elucidated and several theories have been proposed in recent years relating the basic biochemical defect caused by CFTR dysfunction to the CF phenotype. Within the last decade accumulating evidence has suggested that the pulmonary inflammation observed in CF patients may be intrinsically related to the CFTR mutation, resulting in an augmented inflammatory response. This review discusses our changing understanding of the link between CFTR dysfunction and CF lung disease, focusing especially on the role of hyperinflammatory processes. A better understanding of these mechanisms will lead to better treatments for CF and other suppurative lung diseases.

The acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are part of a devastating syndrome characterized by acute onset, hypoxemia, and bilateral infiltrates on chest X-rays. ALI/ARDS arises from the lung's response to local or systemic aggression in which local inflammation and coagulation disorders lead to increased inflammatory pulmonary edema. ARDS is a major cause of morbidity, death, and cost in intensive care units. ALI and ARDS are associated with increased procoagulant and reduced fibrinolytic activities mainly in alveoli and interstitial spaces. Fibrin deposition, which is the hallmark of early phase ALI, stimulates fibroblast aggregation and collagen secretion, contributing to pulmonary fibrosis. The only clinical intervention that has a significant impact on mortality in ARDS is the use of low tidal volume ventilation. ARDS has many coagulation disorders in common with severe sepsis, where recombinant human activated protein C has reduced mortality, hastened improvement in respiratory dysfunction, and shortened the duration of mechanical ventilation. Future clinical trials in ALI/ARDS should evaluate the potential benefits of anticoagulants administered systemically or locally in the lungs.

Surfactant dysfunction has been demonstrated in clinical and experimental studies of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Inflammatory mediators, alveolar exudation, capillary endotheliopathy, and various other mechanisms have been indicted as the cause of surfactant dysfunction. In addition, loss of biophysical activity and damage to the type II alveolar cells leads to altered surfactant production, secretion, and recycling. These factors provide the conceptual rationale for administering exogenous surfactant in ALI/ARDS. Studies of surfactant replacement therapy in ALI/ARDS in children have shown improvement in various parameters of pulmonary function. Multiple simultaneous interventions in the treatment of ALI/ARDS have improved survival and outcomes. The objective of this review is to address the current literature and evidence supporting the administration of exogenous surfactant in the treatment of children with ARDS/ALI.

The use of helium in medicine was first described by Barach who treated obstructive lesions of the airways, in 1936. Since then, only scattered reports can be found in the medical literature until the 80's, when interest in helium resurged for the treatment of acute asthma, as deaths from this disease begun to rise. At least theoretically, because of its physical properties, helium should be useful in several obstructive conditions of the airways including upper airway obstruction, croup, post-extubation stridor, asthma attacks, exacerbations of chronic obstructive pulmonary disease (COPD), etc. However, there is not enough evidence to support the systematic use of heliox to treat severe stages or acute exacerbations of COPD in either ventilated or non ventilated patients because there is currently no convincing impact on patient outcome. Therefore, at present, widespread use of heliox cannot be recommended in clinical practice.

There has been little impact on the incidence of bronchopulmonary dysplasia (BPD) despite advances in perinatal care. BPD is a syndrome of persistent respiratory insufficiency in which preterm infants continue to require supplemental oxygen and/or mechanical ventilatory support with long term implications. Although the severe “classical” form of BPD is infrequently seen, a “new” BPD though often milder continues to complicate the course of the very preterm infant. The aetiology of BPD is likely to be multifactorial, evidence now suggests that premature infants are unable to temper the inflammatory response caused by extra-uterine insults such as mechanical ventilation, sepsis and oxygen. An early increase of pro-inflammatory mediators as well as a concomitant decrease in protective antiinflammatory, antioxidant, anti-protease and growth factors have been noted soon after birth in infants who subsequently develop BPD. This imbalance of inflammation soon after birth is an important factor in the ongoing persistence of BPD and one that requires urgent further research if future preterm infants are to avoid acquiring it. This comprehensive review focuses on this critical imbalance of lung injury and healing in premature infants along with new therapeutic strategies and future implications for research.

Mycobacterium tuberculosis (the causative agent of tuberculosis), is a stealthy pathogen with a great ability to successfully infect humans and a strong will to stay in the host as long as possible. As much as one admires it as a microbiological entity, M. tuberculosis is also a killer at large responsible for an annual death toll of more than two million people worldwide. Treatment of tuberculosis is a lengthy process that requires multiple drugs for at least six months and although a worldwide health policies established by World Health Organization (WHO) helped reducing the rate of treatment failure, the appearance of novel forms of drug- resistant M. tuberculosis has become a major issue during the last years. The advances in the knowledge of the genetics of this pathogen have allowed for a better understanding of its physiology which in turn helped unveiling the mechanisms of drug action and the ensuing mechanisms of resistance. Surprisingly, it was found that most of the specific anti-tubercular drugs target the synthesis of mycolic acids, long chain fatty acids that are essential components of the cell wall structure. This review highlights the studies on anti-tubercular agents that abrogate the synthesis of mycolic acids with special emphasis on molecules that might be added to the therapeutic weaponry to treat tuberculosis.