Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms.

Bronchiectasis is a chronic and debilitating lung disease, characterised by irreversible dilatation of the bronchi as consequence of airway injury and remodelling due to recurrent or chronic airway inflammation and infection. The underlying aetiologies include autoimmune diseases, severe infections, genetic abnormalities and acquired disorders. The pathogenesis of bronchiectasis is poorly understood. Three distinct pathogenetic elements, namely infection, inflammation and enzymatic actions, which interact with each other, have been implicated in the pathophysiology of bronchiectasis. Some recent observations indicate that airway inflammation in bronchiectasis comes from a deregulated cytokine network independent of bacterial airway colonisation. In the present review, current knowledge about cellular and molecular inflammatory events in the dynamic process of host-pathogen interaction that are thought to play a relevant role in the pathogenic mechanisms of airway wall destruction leading to bronchiectasis are discussed.

Persistent airway inflammation and high exacerbation rate in asthma that starts at menopause.

BACKGROUND AND AIM: Asthma that begins around the time of menopause is frequently characterised by marked clinical severity and poor response to treatment. We sought to assess the clinical characteristics, bronchial responsiveness, perception of induced bronchoconstriction and airway inflammation in women with menopausal asthma, as compared to women of a similar age with pre-existing asthma. METHODS: Nine women with pre-existing asthma were selected for clinical severity (symptoms, lung function and medication requirements) similar to that in 11 women with menopausal asthma. Anti-asthmatic treatment in all of the study patients included high dose inhaled (with or without oral) corticosteroids. RESULTS: The women with menopausal asthma demonstrated less atopy, more chronic recurrent sinusitis, similar airway responsiveness, and similar perception of induced bronchoconstriction, but a significantly higher sputum eosinophil count (19.5 +/- 10.8 versus 3.3 +/- 4.3%; p < 0.001) and a higher severe exacerbation rate during the 1-year follow-up period (5.09 +/- 4.85 versus 0.78 +/- 0.97; p < 0.05). Sputum eosinophil count and severe asthma exacerbation rate correlated well in both groups considered as a whole (r = 0.65; p < 0.005). CONCLUSION: The eosinophilic airway inflammation present in women with menopausal asthma is poorly responsive to anti-inflammatory treatment with corticosteroids and predisposes to frequent severe exacerbations. Airway inflammation should be monitored in women with menopausal asthma.

Euthyroid goitre and sleep apnea.

A number of predisposing factors (obesity, nasal obstruction, adenoidal hypertrophy, macroglossia, etc) have been related to obstructive sleep apnea syndrome (OSAS). In addition hypothyroidism and large goitres have been reported to be associated to OSAS, but this association has not been adequately studied. We describe an obese patient with euthyroid goitre associated with OSAS. The patient showed a body mass index (BMI) of 47 and a large neck with a circumference of 60 cm. The flow-volume curve demonstrated an expiratory plateau suggesting an intrathoracic upper airway obstruction. Arterial blood gas analysis results were: pH 7.39; PCO2 54.2 mmHg; P O2 47 mmHg. Nocturnal polisomnography showed an apnea/hypopnea index (AHI) of 31 episodes/hour. Upper airway collapse was overcome by a nasal continuous positive airway pressure (nCPAP) of 14 cmH2O. Weight loss obtained by a hypocaloric diet was not accompanied by any OSAS improvement. After thyroidectomy, a nCPAP of 4 cmH2O was sufficient to prevent upper airway closure. Discontinuation of nCPAP treatment for 4 consecutive nights did not determine worsening of sleep apnea symptoms, nor a worsening of overnight oxymetry. A new polysomnography carried out after 4 nights off nCPAP showed an AHI of 33 episodes/hour. OSAS should be suspected in patients with large goitres. Decisions regarding discontinuation of nCPAP treatment after thyroidectomy should be based on polisomnographic results.

Nocturnal mechanical ventilation improves exercise capacity in kyphoscoliotic patients with respiratory impairment.

BACKGROUND: Patients with severe kyphoscoliosis, with or without stable respiratory failure, frequently experience oxyhaemoglobin desaturation during sleep, exercise, or both. Nasal Intermittent Positive Pressure Ventilation (NIPPV) applied during sleep has been demonstrated to be able to control nocturnal desaturations and also improve diurnal respiratory failure, if this is present, in this group of patients. The aim of this study was to evaluate the effect of a seven-day treatment with nocturnal NIPPV on exercise tolerance in a group of 6 patients with severe kyphoscoliosis and significant nocturnal and exercise-induced oxyhaemoglobin desaturation. METHODS: NIPPV was applied each night for a week by means of a volume cycled pressure ventilator set in assisted/controlled mode. In each patient lung function, daytime arterial blood gas analysis, overnight non invasive recording of arterial saturation, and 6-minutes walking test were carried out initially and at the end of the NIPPV course. RESULTS: During nocturnal NIPPV, as compared to baseline, the percent of night time spent below 90% of oxyhaemoglobin saturation significantly fell from 20 +/- 12.8 to 2.3 +/- 1.9 (Student t-test: p = 0.017). The 6-minute walking distance significantly increased from 244.7 +/- 132.2 to 340 +/- 122.3 m (p = 0.0097). Spirometry, daytime arterial blood gas analysis, and exercise-induced oxyhaemoglobin desaturation were unaffected by treatment. CONCLUSION: A one-week course of treatment with nocturnal NIPPV improves exercise capacity in patients with severe kyphoscoliosis.

Leukotriene receptor antagonists in the treatment of asthma: an update.

Leukotriene receptor antagonists (LTRAs), such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti-inflammatory properties, that make these drugs ideal candidates for the treatment of asthma. The last 1998-updating of the GINA Guidelines for the diagnosis and therapy of asthma recommends the use of LTRAs in the treatment of moderate and mild asthma. In patients with moderate asthma not completely controlled with moderate doses of inhaled corticosteroids, the addition of a LTRA is indicated in alternative to either the increase of the inhaled corticosteroid dose or the addition of an inhaled long-acting beta2-agonist. Both in vitro and in vivo evidences indicate that LTRAs possess an anti-inflammatory activity that is presumably complementary to that presented by corticosteroids. Moreover, clinical studies show that the addition of an LTRA, montelukast, is able to improve clinical and functional indexes in patients with asthma not controlled with inhaled corticosteroids, and to allow a reduction in corticosteroid dosage in patients with asthma well controlled by inhaled corticosteroids. In patients with mild persistent asthma monotherapy with an LTRA is indicated in alternative to a low-dose inhaled corticosteroid, an inhaled cromone, or an oral slow-release theophylline. Previous clinical studies in patients with mild to moderate asthma had demonstrated that monotherapy with LTRAs is able to improve airway function, asthma symptoms, use of as-needed medications, exacerbation rate, and quality of life, without evidence of tolerance with prolonged use. Recently, in a subgroup analysis of patients with mild persistent asthma, a 6-week treatment with oral montelukast or inhaled beclomethasone gave similar improvements in "rescue-free" days, days with well controlled asthma, FEV1, blood eosinophils, beta-agonist use, and nocturnal awakes due to asthma.

Effectiveness and acceptability of a domiciliary multidrug inhalation treatment in elderly patients with chronic airflow obstruction: metered dose inhaler versus jet nebulizer.

The aim of this study was to compare the immediate and long-term bronchodilator effect as well as the patient acceptability of a 2-week, multidrug, inhalation treatment delivered by a metered dose inhaler (MDI) versus a jet nebulizer in a group of elderly patients with chronic obstructive pulmonary disease (COPD) or asthma and an at least partially reversible airflow obstruction. Twenty elderly outpatients (17 men; mean +/- SD age, 67 +/- 2 years; mean +/- SD baseline forced expiratory volume in 1 second [FEV1], 46.5 +/- 14% of predicted value) with COPD or asthma participated in the study, which was of an open, randomized, crossover design. After a 1-day baseline evaluation, including patient history, clinical examination, and spirometry, participants were randomly assigned to receive a multidrug inhalation treatment (a combination of salbutamol, ipratropium, and flunisolide) with either an MDI or a jet nebulizer. Two weeks later, they were shifted to treatment with the alternative system for a further 2 weeks. FEV1 was measured on the first and fourteenth days of each treatment period, on each occasion both before and 30 minutes after the morning inhalation. At the end of the study, patients were asked to express a personal preference for one of the two inhalation treatments with regard to effectiveness and acceptability by filling out a simple questionnaire. Both the MDI and jet nebulizer had a significant immediate bronchodilator effect on the first and fourteenth days of treatment, with no differences between treatments. No long-term bronchodilator effect was seen with either aerosol delivery system. Patient preferences were clearly in favor of the jet nebulizer with regard to effectiveness and in favor of the MDI with regard to acceptability. In conclusion, in elderly patients with COPD or asthma and partially reversible airflow obstruction, a maintenance multidrug bronchodilator/anti-inflammatory inhalation treatment produced a statistically significant and clinically relevant bronchodilator effect without substantial differences between the two delivery systems. Most patients considered the MDI to be more acceptable and the jet nebulizer to be more effective. These preferences should be taken into consideration when prescribing a maintenance aerosol inhalation treatment.