Category Archives: Nonasthmatic chronic

Nonasthmatic chronic cough: DISCUSSION (5)

Airway inflammation

The lack of an effect of budesonide on airway inflammation may be considered to be due to the small number of patients who had successful sputum inductions at each visit. However, this does not seem likely for two reasons. First, we have shown in previous studies significant effects of corticosteroid treatment on sputum indexes within and between small groups of subjects , which were paralleled by improvement in clinical parameters.

Nonasthmatic chronic cough: DISCUSSION (4)

This is the first randomized, controlled trial to examine the effects of treatment with inhaled steroid on cough discomfort as well as inflammatory indexes. Budesonide 800 |ig daily for two or four weeks had no effect. The results emphasize the importance of inclusion of a placebo arm to the treatment because any apparent improvements seen with bu-desonide were matched by placebo.

Nonasthmatic chronic cough: DISCUSSION (3)

Airway inflammation

An unexpected finding was elevated levels of sputum fibrinogen and albumin that we attribute to microvascular leakage. This observation is in line with bronchial biopsies of children with chronic cough showing marked increase in the percentage of area of intercellular spaces denoting airway edema . Increased microvascular leakage is reported in other airway conditions including viral infection and smokers with chronic airflow limitation , conditions also associated with neutrophilia. However, in the present study, it also occurred in some subjects in the absence of abnormal sputum cell counts. IL-8 and other proinflammatory mediators, such as substance P, may be involved. buy diabetes drugs

Nonasthmatic chronic cough: DISCUSSION (2)

They found an increase in mononuclear cells and epithelial cell damage without eosinophilia or neutrophilia. Also, MacGarvey et al, examining the bronchoalveolar lavage fluid of 28 patients with nonasthmatic nonproductive cough due to postnasal syndrome, gastroesophageal reflux or of unknown cause, reported a significant increase in both eosinophils and mast cells. These results, therefore, differ from those in the present study, presumably due to differences in subject selection or in the airway compartments studied. Sputum neutrophilia in the present study was associated with elevated sputum IL-8 levels.

Nonasthmatic chronic cough: DISCUSSION (1)

Airway inflammation

This study demonstrates that chronic cough without asthma or known cause is associated with lower airway inflammation. The inflammatory response was noneosino-philic in all patients and neutrophilic in the majority, and this was accompanied by increased microvascular leakage (as measured by fibrinogen and albumin levels), high levels of IL-8 and substance P, and low levels of ECP. Treatment with inhaled budesonide 800 |ig daily for two or four weeks did not improve cough discomfort or sputum inflammatory indices, possibly because the cause was not associated with sputum eosinophilia. buy prednisone

Nonasthmatic chronic cough: RESULTS (3)

Effect of treatment on cough: Cough discomfort before and after two weeks of treatment with placebo or budesonide was examined. The severity of cough discomfort before treatment did not differ between the treatment groups (Table 1) nor between patients with or without sputum neutrophilia (Table 2). The effects of two weeks treatment with budesonide on cough discomfort, as measured by the VAS, was similar to the placebo effect whether analyzed as the difference between actual values or as the difference between the percentage reduction in cough discomfort (Figure 3). The reduction in cough discomfort after two weeks treatment with open label budesonide was also similar in the two groups.

Nonasthmatic chronic cough: RESULTS (2)

Sputum appearance, cell viability, total and differential cell counts, and the fluid phase measurements of the 32 patients who produced sputum before treatment (Table 2) were examined. In 19 (59%) patients, the proportion and absolute number of neutrophils were above the upper limit for healthy patients. None of the patients had an increase in the proportion or absolute number of eosinophils (0 [0.01]x106/mL). Sputum ECP levels were above the normal range only in seven patients.

Nonasthmatic chronic cough: RESULTS (1)

Randomization and withdrawals: Fifty patients were randomized to one or other study treatment (Figure 1). Twenty-five patients received budesonide and 25 placebo. Two patients (one placebo, one budesonide) were found ineligible after randomization, one because of an abnormal chest radiograph and the other because of documented gastroesophageal reflux; they were withdrawn from the study before the end of the first week. Four other patients (three on budesonide) were withdrawn before the end of the second week of treatment, three due to an intercurrent viral infection (one placebo, two budesonide) and one who did not return. These six patients were excluded from the analysis.

Nonasthmatic chronic cough: PATIENTS AND METHODS (5)

The limits of detection for ECP, fibrinogen, IL-8 and substance P were 2.0 mg/mL, 0.79 mg/L, 25.6 pg/mL and 0.62 pg/mL, respectively. Data analysis: Clinical variables were summarized by means and 95% CI, except for PC20 data, which were log transformed and summarized by geometric mean. Sputum results were summarized by medians and interquartile range.

Nonasthmatic chronic cough: PATIENTS AND METHODS (4)

Airway inflammation

Sputum examination: Sputum was selected from the expectorate and processed as described elsewhere. The success of the selection was confirmed by a proportion of squamous epithelial cells of 5% or less. The concentration of ECP (|ig/L) in the thawed supernatant was determinated using a sensitive radioimmunoassay (RIA, Kabi Pharmacia Diagnostics AB, Uppsala, Sweden).

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