Near-fatal asthma phenotype in the ENFUMOSA Cohort.

BACKGROUND: Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. METHODS: The aim of our study was to compare the clinical, functional and inflammatory characteristics of NFA patients with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic patients from five centres of the European Network for Understanding Mechanisms of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite treatment with high doses of inhaled corticosteroids, long-acting beta2-agonists and for 1/3 also with regular oral corticosteroids, had at least one asthma exacerbation in the previous year; 24 with an NFA episode in the previous 5 years in the absence of inclusion criteria for the previous groups. All the patients were examined in stable conditions. RESULTS: NFA patients were taking less corticosteroids and were less compliant to prescribed asthma medications than the other two groups of patients. Lung function, blood gases, atopic status, sputum and blood inflammatory cell count of NFA patients were similar to mild-to-moderate, but not severe, asthmatic patients. CONCLUSIONS: In stable conditions patients with an NFA attack in the previous 5 years cannot be distinguished from patients with mild-to-moderate asthma, while they are different from severe asthmatics both in terms of lung function and of airway inflammation. The risk factor that characterizes this group of patients is reduced usage of prophylactic corticosteroids.

Comparison of allergen immunotherapy and drug treatment in seasonal rhinoconjunctivitis: a 3-years study.

Drug treatment and specific immunotherapy (SIT) are both effective in seasonal rhinoconjunctivitis, but the former acts only on allergic symptoms while the latter modifies the natural history of the disease. Only a few studies compared the clinical efficacy of the two treatments with contrasting results. We planned a study to compare the efficacy of SIT (15 patients) and drug treatment (15 patients) in moderate to severe seasonal rhinoconjunctivitis caused by sensitization to grass pollen. SIT was performed by a 5-grass extract standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergénes, Antony, France) using the conventional build-up phase in 12 weeks and a maintenance treatment with monthly injection for three years. Drug treatment was done with cetirizine as antihistamine, mometasone furoate as nasal topical steroid, and levocabastine eyedrops. All patients registered during the pollen season their symptoms and drug consumption. After one year 12 of 15 patients treated with SIT had less symptoms and drug consumption in respect to baseline compared to none in drug treated group (p = 0.021) and after three years 15 of 15 were improved in group A compared to one of 15 in group B (p = 0.008). These findings indicate an higher efficacy of SIT in patients with seasonal rhinitis not only in the long term but also in the first year of treatment.

Predominant emphysema phenotype in chronic obstructive pulmonary.

Patients with fixed airflow limitation are grouped under the heading of chronic obstructive pulmonary disease (COPD). The authors investigated whether COPD patients have distinct functional, radiological and sputum cells characteristics depending on the presence or absence of emphysema. Twenty-four COPD outpatients, 12 with and 12 without emphysema on high-resolution computed tomography scan of the chest, were examined. Patients underwent chest radiography, pulmonary function tests and sputum induction and analysis. Subjects with documented emphysema had lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio, and lower carbon monoxide diffusion constant (K(CO)), compared with subjects without emphysema. Chest radiograph score of emphysema was higher, chest radiograph score of chronic bronchitis was lower, and the number of sputum lymphocytes was increased in patients with emphysema, who also showed a negative correlation between K(CO) and pack-yrs. Chronic obstructive pulmonary disease patients with emphysema, documented by high-resolution computed tomography scan, have a different disease phenotype compared with patients without emphysema. Identification of chronic obstructive pulmonary disease-related phenotypes may improve understanding of the natural history and treatment of the disease.

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers.

BACKGROUND: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. METHODS: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. RESULTS: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2 (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36-40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. CONCLUSIONS: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.

Pulmonary blastoma: case report in an adult.

We present a case of biphasic pulmonary blastoma, a rare primary malignant lung neoplasm, in a 48 year old man. Despite its resection followed by postoperative chemotherapy, the neoplasm recurred and the patient survived only 41 months after the diagnosis.

Congenital diaphragmatic hernia in an adult simulating a pleural liposarcoma.

We report the case of a 32-year-old man with the onset of exercise-related dyspnea, chest pain and chest radiography simulating a pleural effusion. The computed tomography of the chest showed signs suggesting pleural liposarcoma. Because of these findings, a videothoracoscopy was performed which surprisingly showed the presence in the left pleural space of intrapleural omentum and spleen. This report underlines that the clinical manifestations of Bochdalek hernia in adults are variegate and in most cases preoperative diagnosis is not possible.

Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease.

We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV(1) of < 12% and < 200 ml after 200 microg of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV(1) of < 12% but > 200 ml after 200 microg of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.

Goblet cell hyperplasia and epithelial inflammation in peripheral airways of smokers with both symptoms of chronic bronchitis and chronic airflow limitation.

To quantify the number of goblet cells and inflammatory cells in the epithelium of peripheral airways in smokers with both symptoms of chronic bronchitis and chronic airflow limitation, we examined surgical specimens obtained from 25 subjects undergoing lung resection for localized pulmonary lesions: 10 smokers with symptoms of chronic bronchitis and chronic airflow limitation, six asymptomatic smokers with normal lung function, and nine nonsmoking control subjects. Peripheral airways were examined with histochemical methods to identify goblet cells and with immunohistochemical methods to identify total leukocytes (CD45(+) cells), neutrophils, macrophages, CD4(+) and CD8(+) cells in the epithelium. When compared with nonsmokers, smokers with both symptoms of chronic bronchitis and chronic airflow limitation had an increased number of goblet cells (p < 0.01), CD45(+) cells (p < 0. 01), macrophages (p < 0.05), and CD8(+) cells (p < 0.01) in the epithelium of peripheral airways. When all the smokers were grouped together, they showed an increased number of neutrophils (p < 0.05) along with an increased number of goblet cells, CD45(+) cells, macrophages and CD8(+) cells (p < 0.05) compared with nonsmokers. In conclusion, smokers with both symptoms of chronic bronchitis and chronic airflow limitation have an increased number of goblet cells and inflammatory cells in the epithelium of peripheral airways.

The distribution of neurokinin-1 and neurokinin-2 receptors in human central airways.

The precise locations of neurokinin (NK)-1 and NK-2 receptors in human airways, and their role in airway inflammatory diseases, have not been carefully examined. To determine the distribution of NK-1 and NK-2 receptors in human central airways, and to determine whether their distribution was different in smokers, we examined surgical specimens from patients undergoing lung resection for limited lung lesions. We mapped NK-1 and NK-2 receptors in four groups of subjects: four asymptomatic nonsmokers, seven asymptomatic smokers, seven symptomatic smokers with normal lung function, and eight symptomatic smokers with chronic airflow limitation. Tissues were immunostained with anti-NK-1- and anti-NK-2-receptor antibodies. Expression of NK-1 and NK-2 receptors was quantified through light microscopy and image analysis. Both NK-1 and NK-2 receptors were found in bronchial glands, bronchial vessels, and bronchial smooth muscle. Although no receptors were observed in the epithelium, receptors were occasionally found in nerves (NK-1) and in inflammatory cells (NK-2) such as T lymphocytes, macrophages, and mast cells. The distribution of both NK-1 and NK-2 receptors was similar in all the tissues examined in the four groups of subjects. These data show that NK-1 and NK-2 receptors are present in human central airways and that their expression is not modified by cigarette smoking.

CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease.

Previous studies have shown an increased number of inflammatory cells and, in particular, CD8+ve cells in the airways of smokers with chronic obstructive pulmonary disease (COPD). In this study we investigated whether a similar inflammatory process is also present in the lungs, and particularly in lung parenchyma and pulmonary arteries. We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: nonsmokers (n = 8), asymptomatic smokers with normal lung function (n = 6), and smokers with COPD (n = 10). Alveolar walls and pulmonary arteries were examined with immunohistochemical methods to identify neutrophils, eosinophils, mast cells, macrophages, and CD4+ve and CD8+ve cells. Smokers with COPD had an increased number of CD8+ve cells in both lung parenchyma (p < 0.05) and pulmonary arteries (p < 0.001) as compared with nonsmokers. CD8+ve cells were also increased in pulmonary arteries of smokers with COPD as compared with smokers with normal lung function (p < 0.01). Other inflammatory cells were no different among the three groups. The number of CD8+ve cells in both lung parenchyma and pulmonary arteries was significantly correlated with the degree of airflow limitation in smokers. These results show that an inflammatory process similar to that present in the conducting airways is also present in lung parenchyma and pulmonary arteries of smokers with COPD.