Tag Archives: COPD

Canadian Neighbor Pharmacy: Use of Calcium Channel Blockers in Hypoxic Lung Disease

vasodilatorsThe rationale for considering the combined use of vasodilators and low-flow oxygen in patients with COPD and hypoxemia is based on five hypotheses. The extent to which these hypotheses are correct will likely determine the long-term usefulness of vasodilators in these patients.

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Structural Changes in Airway Diseases: Conclusions

Various methodologic aspects should, however, be taken into account when studying these effects.
For example, some agents could possibly be more effective at preventing than reversing airway remodeling, and the duration of treatment and doses of the agents should be considered, as well as the type and duration of the disease. Research on gene therapy in lung diseases is currently under scrutiny. Other than CF or a1-antitrypsin deficiency, it is highly unlikely that a single vector will be therapeutic, as multiple genes are implicated in asthma and COPD diseases. Gene therapy has been studied mostly in relation to CF. Vectors and incorporating techniques need to be optimized to prove helpful in treatment of CF patients. Overall, primary prevention of airway disease is likely to be the most effective tool and can be achieved by allergen avoidance, smoking avoidance, control of infections, or prenatal diagnosis. Treatment of other allergic diseases might possibly prevent the development of asthma, especially in allergic rhinitic subjects and in subjects with asymptomatic AHR and has to be further studied.

Although this is still controversial, we have evidence that the airway remodeling process may have untoward consequences in obstructive diseases, in the clinical expression of the disease, in its development, and in the decline in pulmonary function. The common factor underlying all the structural changes in airway diseases is an injury/repair process. In asthma, the damage follows an allergenic or nonal-lergenic Th2 inflammation and mechanical stress. In COPD, the initial trigger is cigarette smoke inducing direct cell toxicity and inflammatory response. An infectious process is both at the origin of the inflammation observed in CF and bronchiectasis patients. More research should be done to identify key changes, effective treatments, and proper interventional timing to counteract these changes. The prevention of the development of asthma, COPD, or other airway diseases through early interventions on structural changes is an exciting avenue. The potential of novel therapeutic agents to reverse or prevent airway remodeling warrants further evaluation.

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.
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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

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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

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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.
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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.
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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

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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

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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

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