Little is known about the treatment and correlates of dyspnea in idiopathic pulmonary fibrosis (IPF).

OBJECTIVES: The objective of this systematic review was to summarize the literature regarding the treatment and correlates of dyspnea in IPF.

METHODS: MEDLINE, EMBASE, and all Evidence-Based Medicine Reviews were searched for publications that evaluated treatment or correlates of dyspnea in IPF. Reference lists and recent review articles also were searched.

RESULTS: The heterogeneity of included studies did not permit meta-analysis. Dyspnea improved in studies of sildenafil, pulmonary rehabilitation, and prednisone with colchicine. Additional studies of these three treatments, however, found discordant results. One study suggested that assisted ventilation delivered by facemask improved exertional dyspnea. Oxygen and opioids improve dyspnea in other chronic lung diseases, but data in IPF are limited. Correlates of dyspnea included functional and physiological measures and comorbid diseases.

CONCLUSION: Sildenafil and pulmonary rehabilitation should be considered as potential therapies for dyspnea in selected patients with IPF. Supplemental oxygen and opioids may be additional potential therapies; however, the evidence supporting their use is weak. Additional research should focus on the management of functional status and comorbidities as potential treatments for dyspnea.

To evaluate whether asthma and airway hyper-responsiveness are associated with HIV infection.

METHODS: We reviewed the literature on HIV-associated pulmonary diseases, pulmonary symptoms, and immune changes which may play a role in asthma. The information was analyzed comparing the pre-HAART era to the post-HAART era data.

RESULTS: HIV-seropositive individuals commonly experience respiratory complaints yet it is unclear if the frequency of these complaints have changed with the initiation of HAART. Changes in pulmonary function testing and serum IgE are seen with HIV infection even in the post-HAART era. An increased prevalence of asthma among HIV-seropositive children treated with HAART has been reported.

CONCLUSION: The spectrum of HIV-associated pulmonary disease has changed with the introduction of HAART. Current data is limited to determine if asthma and airway hyper-responsiveness are more common among HIV-seropositive individuals treated with HAART.

Reduction of lung inflammation is one of the goals of cystic fibrosis (CF) therapy. Among anti-inflammatory molecules, glucocorticoids (GC) are one of the most prescribed. However, CF patients seem to be resistant to glucocorticoid treatment.

Several molecular mechanisms that contribute to decrease anti-inflammatory effects of glucocorticoids have been identified in pulmonary diseases, but the molecular actions of glucocorticoids have never been studied in CF. In the cytoplasm, glucocorticoids bind to glucocorticoid receptor (GR) and then, control NF-κB and MAPK pathways through direct interaction with AP-1 and NF-κB in the nucleus. Conversely, MAPK can regulate glucocorticoid activation by targeting GR phosphorylation. Together these pathways regulate IL-8 release in the lung. Using bronchial epithelial cell lines derived from non CF and CF patients, we analyzed GR-based effects of glucocorticoids on NF-κB and MAPK pathways, after stimulation with TNF-α.

We demonstrate that the synthetic glucocorticoid dexamethasone (Dex) significantly decreases IL-8 secretion and AP-1 or NF-κB activity in CF cells in a pro-inflammatory context. Moreover, we show that p38 MAPK controls IL-8 release by determining GR activation through specific phosphorylation on serine 211. Finally, we demonstrate a synergistic effect of dexamethasone treatment and inhibition of p38 inducing more than 90% inhibition of IL-8 production in CF cells.

All together, these results demonstrate the good responsiveness to glucocorticoids of CF bronchial epithelial cells and the reciprocal link between glucocorticoids and p38 MAPK in the control of CF lung inflammation.

Computed tomography (CT) is a clinical tool widely used to assess and followup asthma and chonic obstructive pulmonary disease (COPD) in humans. Strong efforts have been made the last decade to improve this technique as a quantitative research tool. Using semiautomatic softwares, quantification of airway wall thickness, lumen area, and bronchial wall density are available from large to intermediate conductive airways.

Skeletonization of the bronchial tree can be built to assess its three-dimensional geometry. Lung parenchyma density can be analysed as a surrogate of small airway disease and emphysema. Since resident cells involve airway wall and lung parenchyma abnormalities, CT provides an accurate and reliable research tool to assess their role in vivo.

This litterature review highlights the most recent advances made to assess asthma and COPD with CT, and also their drawbacks and the place of CT in clarifying the complex physiopathology of both diseases.