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Interstitial lung disease in systemic sclerosis.

Despite many unanswered questions regarding the pathogenesis of interstitial lung disease in systemic sclerosis (SSc-ILD) and the lack of accurate epidemiological risk factors, there have been major advances in the identification and prognostic evaluation of SSc-ILD.

The evaluation of disease severity is a multidisciplinary exercise, requiring the integration of pulmonary function tests, high-resolution computed tomography data, and symptomatic severity and these factors all need to be considered in the detection of disease progression. Except in a minority of patients with reversible inflammatory disease, the primary goal of treatment is the prevention of disease progression. Current treatment regimens are cente...

Cross-disciplinary collaboration in connective tissue disease-related lung disease.

Lung disease is a common manifestation of connective tissue disease (CTD) and is associated with significant morbidity and mortality. The evaluation of lung disease, and interstitial lung disease (ILD) in particular, in patients with CTD is complex because of the heterogeneity of the CTDs, the varied types and degrees of severity of ILD encountered, and because ILD can be identified at any point in time in these patients.

Cross-disciplinary, thorough evaluations are needed when CTD patients develop ILD or when evaluating ILD patients for the presence of occult CTD. Determining that ILD is associated with an established CTD requires the exclusion of alternative etiologies, and thorough assessments of the clinical features of both the CTD and I...

Therapy of chronic urticaria: a simple, modern approach.

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OBJECTIVE: To examine the available treatment choices for chronic spontaneous urticaria (CSU) and discuss a new paradigm for treating such patients.
DATA SOURCES: The literature regarding treatment is reviewed, including considerations of published guidelines. Attention is focused on the most recent evidence indicating particular efficacy of omalizumab.

RESULTS: Omalizumab has been found to have considerable efficacy in phase 2 and phase 3 trials in which more than 900 patients have been studied. A response rate of 65% is seen in patients resistant to antihistamines as well as to histamine2 blockers and leukotriene antagonists, and 40% of patients are completely free of hives as long as therapy is continued. In addition, serious adverse events have not been seen. Only cyclosporine can match this response rate (excluding steroids), but the adverse effect profile (blood pressure and renal function) is substantial by comparison. Double-blind, placebo-controlled studies of other agents often listed as alternatives are lacking (ie, whether their success rate exceeds the 25%-30% placebo response is uncertain). The mechanism by which omalizumab works in CSU is not clear because the response rate is unrelated to the autoimmune profile and can occur rapidly (ie, within a few days).

CONCLUSION: Omalizumab has exceptional efficacy for antihistamine-resistant CSU with an excellent adverse effect profile.

Regulation of pulmonary inflammation by mesenchymal cells.

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Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue remodelling, but also have an important role in pulmonary inflammation.

This review will describe the immunomodulatory functions of pulmonary mesenchymal cells, such as airway smooth muscle (ASM) cells and lung fibroblasts, in chronic respiratory disease. An important theme of the review is that pulmonary mesenchymal cells not only respond to inflammatory mediators, but also produce their own mediators, whether pro-inflammatory or pro-resolving, which influence the quantity and quality of the lung immune response. The notion that defective pro-inflammatory or pro-resolving signalling in these cells potentially contributes to disease progression is also discussed.

Finally, the concept of specifically targeting pulmonary mesenchymal cell immunomodulatory function to improve therapeutic control of chronic respiratory disease is considered.

Meta-Review: Adverse Effects of Inhaled Corticosteroids Relevant to Older Patients.

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In recent years, clinical trials and observational studies have raised concerns about the potential adverse effects of inhaled corticosteroids (ICS) such as pneumonia, cataract, fractures and hyperglycaemia, which are of particular concern for older patients.

METHODS: We conducted a meta-review by searching electronic databases (MEDLINE, EMBASE, PubMed) for systematic reviews and meta-analyses of ICS use and the adverse effects of interest. We also evaluated new primary studies that reported information beyond that available from previously published meta-analyses. Two reviewers independently extracted data on measures of associated harm with ICS use.

RESULTS: We identified five relevant meta-analyses for inclusion in this meta-review, and also three new studies of ICS and pneumonia. We found consistent evidence of a dose-response relationship between ICS use and serious adverse effects such as fractures and pneumonia. The estimated number needed to treat for harm due to fracture with ICS was 83 with 3-years use, and 60 per year for pneumonia. Both asthma and chronic obstructive pulmonary disease (COPD) users of ICS were at risk of pneumonia, with fluticasone appearing to confer higher risk than budesonide. There is also some suggestion that ICS use is associated with cataracts in a dose-response manner but the evidence is less robust here. Equally, the influence of ICS on diabetes mellitus remains uncertain.

CONCLUSIONS: In view of the dose-response relationship seen between ICS use and important adverse effects such as fractures and pneumonia, clinicians needs to carefully balance the benefits of ICS versus the harms in older patients receiving long-term high-dose ICS.

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