Category Archives: Pulmonary Function

Structural Changes in Airway Diseases: Remaining Questions and Future Research

Structural Changes in Airway Diseases: Remaining Questions and Future ResearchPhosphodiesterase Inhibitors: Selective phosphodiesterase inhibitors have been designed and studied, mainly in COPD. The breakdown of intracellular cyclic adenosine monophosphate following phosphodiesterase inhibition has been suggested to explain bronchodilatory and antiinflammatory effects and could lead to potential antiremodeling properties. The phosphodiesterase-3 inhibitor siguazodan has been shown to reduce in vitro proliferation of human ASM. In addition, the phosphodiesterase-4 inhibitor roflumilast reduced inflammation, subepithelial collagen deposition, and thickening of airway epithelium in an asthma mouse model. More info

Continue reading

Structural Changes in Airway Diseases: Antiremodeling Property

Monoclonal antibodies against IL-5 were shown to be effective in reducing the deposition of ECM proteins tenascin, lumican, and procollagen in the basement membrane of patients with mild asthma. In addition, anti-IL-5 reduces blood and sputum eosinophilia. Subepithelial fibrosis prevention has been observed with anti-IL-5 in a mouse model of asthma. These data suggest that these agents may influence remodeling, which might be partly preventable or reversible.
Continue reading

Structural Changes in Airway Diseases: Immunosuppressors

Structural Changes in Airway Diseases: ImmunosuppressorsMethotrexate is a folic acid antagonist that inhibits thymidine synthesis and thereby interferes with DNA synthesis. There is no consensus on the use of methotrexate in asthma, and nothing is known about its effects on remodeling. Azathioprine has no proven benefit in asthma. Cyclosporin A has inhibitory effects on mast cells, monocytes, neutrophils, basophils, and T-cells, and might have some benefit in severe corticosteroid-dependent asthma but no effect on remodeling has been described in hu-mans. However, in a cat model of asthma, cyclo-sporine A decreased inflammation and remodeling processes such as ASM hypertrophia and goblet-cell and submucosal gland hyperplasia. IV Igs have antiinflammatory properties as well; they may decrease the use of corticosteroids and reduce respiratory symptoms. Potential antiremodeling effects have not been assessed. add comment

Continue reading

Structural Changes in Airway Diseases: B2-Adrenoreceptors Agonists and Theophylline

In vivo, epithelial cells express fewer adhesion molecules after second-generation antihistamine treatment. In a murine model of asthma, antihistamines inhibited the Th2 response, lung inflammation, and AHR. Antihistamines further afforded broncho-protection against methacholine challenge. Antihistamines could possibly be useful in preventing the development of asthma in certain patients as reported in cohorts of children with atopic dermatitis. Other antiallergic molecules such as cromolyn and nedocromil stabilize mast-cell membrane and therefore decrease mediator release. Although it might be of interest to determine whether they could play a role in the prevention of remodeling, up to now we have no data indicating that they may affect bronchial structural changes (Table 3). in detail

Continue reading

Structural Changes in Airway Diseases: Effect of Corticosteroids on Vascular Alterations

Structural Changes in Airway Diseases: Effect of Corticosteroids on Vascular AlterationsA low MMP-9/TIMP-1 ratio suggested a predominant fibrogenic process over the inflammatory process, explaining the poor efficiency of corticosteroids. Duration of treatment and asthma severity seemed to modulate the effect of corticosteroids on MMP/TIMP. Finally, in COPD, high doses of ICS had no effect on sputum elastase, MMP-1, MMP-9, SLPI, or TIMP-1 levels.
Continue reading

Structural Changes in Airway Diseases: Profibrotic effect

This finding has led to the hypothesis that ICS might be effective in reducing RBM thickness when used for a long period of time and at a higher dose. In a group of patients with moderate-to-severe asthma, no significant differences were seen in types I and III collagen and TGF-^ immunoreactivity after a 2-week course of oral corticosteroids. The inability of ICS to inhibit TGF-^ expression may be responsible for the persistent fibrosis seen in this group of patients with severe asthma. The fact that doses of  ICS could have been too low and the duration of treatment could have been too short has been suggested as an explanation for the poor response.
Continue reading

Structural Changes in Airway Diseases: Effect of Corticosteroids on ECM Components

Structural Changes in Airway Diseases: Effect of Corticosteroids on ECM ComponentsFuture studies will help us to understand the precise effect of corticosteroids on fibroblasts.
In vitro studies of the use of corticosteroids show a decrease in smooth-muscle cell proliferation. The antiproliferative effect of corticosteroids can therefore benefit asthmatic patients through smooth-muscle mass reduction if it is also effective in vivo. As smooth-muscle cells produce inflammatory mediators, corticosteroids can also reduce cytokine and chemokine production at this level, but this has to be confirmed. Some studies have shown that corticosteroids have no effect on the activation of the nuclear factor-кБ transcription factor, suggesting a possible immunosuppressive effect by corticosteroids on ASM. Corticosteroids were also ineffective in reducing ECM protein production by human ASM. Thus, corticosteroids may improve asthma control through decreased smooth-muscle cell proliferation but are less effective in modulating the synthesis of ECM proteins and cytokines. add comment

Continue reading

Structural Changes in Airway Diseases: Mucus Production

In COPD, it was reported that high doses of ICS had no effect on sputum inflammatory cell number, IL-8 levels, elastase activity, MMP-1, MMP-9, SLPI, or TIMP-1. Systemic corticosteroids are used in a short-course pattern in exacerbated COPD, improving lung function and clinical outcomes. However, the antiinflammatory effect of such a short course of systemic corticosteroid treatment has not been addressed in COPD patients. As CD4+ T-cells and mast cells have not been linked to COPD inflammation, there are no convincing data on the potential therapeutic role of corticosteroids in COPD with the exception of exacerbated COPD and COPD with increased eosino-phils. In CF, ICS failed to reduce airway inflammation. In bronchiectasis, corticosteroids decreased T-cell infiltration and IL-8 levels, but clinical benefits are still not clear. more

Continue reading

Structural Changes in Airway Diseases: Progression of the Disease

Structural Changes in Airway Diseases: Progression of the DiseaseHowever, the Childhood Asthma Management Program study reported no significant long-term prevention in the decline of lung function with ICS in children presenting mild-to-moderate asthma. Whether the decline in lung function is preventable in asthma needs to be confirmed. ICS has no effect on FEV1 decline, respiratory symptoms and exacerbations in mild to moderate COPD, while in moderate to severe COPD, a positive effect is seen. This reflects the facts that inflammation in COPD is different from asthma-associated inflammation and that damages are mostly irreversible. In CF, oral corticosteroids appear to slow the progression of the disease. review

Continue reading

Structural Changes in Airway Diseases: Corticosteroids

What Is the Clinical Relevance of Airway Remodeling? Many of the changes described above are part of an abnormal or exaggerated response to an airway insult, and the type and time-course of these alterations will vary according to the type of offending agent, the duration of the process, and the genetic predisposition of the individual for such a response. Airway remodeling, as bronchial inflammation, may be observed in the absence of clinical manifestations, and there may be a threshold after which their combined influence on airway function will be sufficient to induce respiratory symptoms; in asthma, this may occur after a period of subclinical AHR. Reading here

Continue reading