Platelet activation and cardiovascular co-morbidities in patients with chronic obstructive pulmonary disease.

Objective: Platelet activation in COPD patients is associated with an increased risk of cardiovascular events. Aim of the study: to assess the mean platelet volume (MPV), as an index of platelet activation, in patients with COPD both when stable or during exacerbation. Research design and methods: 478 patients with COPD (75 with exacerbation) and 72 age-matched healthy controls were enrolled. Medical history, co-morbidities, medications, pulmonary function tests, MPV and blood cell count, erythrocyte sedimentation rate (ERS) and C reactive protein (CRP) were recorded. Results: MPV was higher in COPD patients than in controls (8.7 \ub1 1.1 fL and 8.4 \ub1 0.8 fL respectively, p = 0.025) and increased across the severity of the diseases as assessed by the GOLD post bronchodilator FEV1 categorized I to IV (p>0.05). MPV was higher in COPD patients during acute exacerbation as compared with stable condition (8.7 \ub1 1.0 fL and 8.9 \ub1 1.0 fL, p = 0.021). MPV 65 10.5 fL correlated with the presence of at least one co-existing cardiovascular disease (p = 0.008) . No correlation was observed between MPV and CRP or ERS in patients or in controls. An inverse significant correlation was found between platelets count and MPV in COPD patients. Conclusions: Elevated MPV is associated with lower platelet count and with cardiovascular co-morbidity in COPD patients. MPV value is higher in more severe COPD and during acute exacerbation. Present findings warrant future studies to confirm a possible clinically relevant role for platelet activation and cardiovascular risk in the population of COPD

Exhaled nitric oxide in patients with PiZZ Phenotype-related α 1-anti-trypsin deficiency

AbstractThere is no report of exhaled NO (eNO) in subjects with different phenotypes ofα1 -anti-trypsin (AAT) deficiency.Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFENO]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n=25; PiSZ n=6; PiZZ, n=9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20FEV1) was also assessed.plFENOwas significantly lower in the PiZZ group (4·5±1·4 ppb) than in matched PiMM subjects (8·2±3·8 ppb), in healthy controls (9·3±2·8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DLCOwere significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes.These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects

Kaposi's disease and sarcoidosis

A human immunodeficiency virus (HIV) antibody-negative 65 year old woman was treated with corticosteroids for 7 yrs because of bilateral uveitis. One year after the beginning of corticosteroid treatment, erythematous skin lesions appeared on the legs. Eight years after the diagnosis of uveitis, gastric and bronchial biopsies revealed noncaseating epithelioid cell granulomas, whilst a cutaneous biopsy showed Kaposi's disease. Sarcoidosis-associated alteration of immune regulation and corticosteroid therapy may have promoted the development of disease

Single inhaler LABA/LAMA for COPD

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field

Exhaled nitric oxide as a marker of lung involvement in Crohns disease.

Crohn’s Disease (CD) is an inflammatory bowel disease that is often associated with a variety of systemic manifestations, including airways involvement. The latter is in most cases subclinical, and requires expensive and invasive methods to be diagnosed. Fractional Exhaled Nitric Oxide (FENO) can be measured non invasively at low (bronchial air) and high (alveolar air) flows to reflect proximal airway inflammation, and systemic inflammation. The aim of our study was to compare both bronchial and alveolar FENO as an index of pulmonary involvement and of systemic inflammation in CD patients with at different stages of clinical activity and different treatments, with a group of healthy subjects studied. Thirty CD patients (age 43.10 ± 14.6 yrs) without clinical evidence of pulmonary diseases and 21 non smokers, not atopic healthy controls (age 35.1 ± 13.2 yrs) were enrolled. FENO was measured using a chemiluminescence analyzer at high and low flows. Bronchial (14.9 ± 10.2 ppb vs 10.1 ± 6.3 ppb, p=0.049) and alveolar FENO (4.4 ± 2.2 ppb vs 2.6 ± 1.9; p=0.006) were significantly higher in Crohn’s disease than in healthy controls, respectively, and bronchial FENO was significantly higher in CD patients treated with immunomodulators (20.4 + 11.5 ppb) than in those treated with mesalazine (7.9 + 4.2 ppb, p=0.04). Both bronchial (p=0.0016) and alveolar FENO (p=0.017) were positively correlated with Crohn’s Disease Activity Index. In conclusion, our results for bronchial FENO confirm subclinical pulmonary involvement in Crohn’s disease. Alveolar FENO may be of clinical value during follow-up of these patients as a surrogate marker of systemic inflammatio

EXHALED NITRIC OXIDE AS A MARKER OF LUNG INVOLVEMENT IN CROHN'S DISEASE

Crohn's Disease is an inflammatory bowel disease associated with a variety of systemic manifestations, including large and small airway involvement. The latter is most often a subclinical one, and requires expensive and invasive diagnostic approaches. Nitric Oxide (NO) can be detected non-invasively in the exhaled air (eNO) and be considered as a surrogate marker of airway inflammation. eNO tested at multiple expiratory flows can be used to distinguish the alveolar concentration of NO (CalvNO) from the total amount of fractional eNO (FeNO). The aim of our study is to compare FeNO and concentration of alveolar nitric oxide (CalvNO) levels and to assess their relationship with pulmonary involvement in Crohn's patients differing in clinical stage and therapeutic regimens versus a group of healthy subjects. Thirty Crohn's patients not showing clinical evidence of pulmonary diseases and 21 non-smoking, non-atopic healthy controls were enrolled. FeNO (14.9\ub110.2 ppb vs 10.1\ub16.3 ppb, p=0.049) and CalvNO (4.4\ub12.2 ppb vs 2.6\ub11.9; p=0.006) values were found to be significantly higher in Crohn's patients than in healthy controls. Both FeNO and CalvNO correlated positively with the Crohn's Disease Activity Index. In conclusion, our results for FeNO and CalvNO confirm the presence of subclinical pulmonary involvement in Crohn's disease. eNO measurement may be of clinical value in the follow-up of Crohn's patients.Crohn's Disease is an inflammatory bowel disease associated with a variety of systemic manifestations, including large and small airway involvement. The latter is most often a subclinical one, and requires expensive and invasive diagnostic approaches. Nitric Oxide (NO) can be detected non-invasively in the exhaled air (eNO) and be considered as a surrogate marker of airway inflammation. eNO tested at multiple expiratory flows can be used to distinguish the alveolar concentration of NO (CalvNO) from the total amount of fractional eNO (FeNO). The aim of our study is to compare FeNO and concentration of alveolar nitric oxide (CalvNO) levels and to assess their relationship with pulmonary involvement in Crohn's patients differing in clinical stage and therapeutic regimens versus a group of healthy subjects. Thirty Crohn's patients not showing clinical evidence of pulmonary diseases and 21 non-smoking, non-atopic healthy controls were enrolled. FeNO (14.9 +/- 10.2 ppb vs 10.1 +/- 6.3 ppb, p=0.049) and CalvNO (4.4 +/- 2.2 ppb vs 2.6 +/- 1.9; p=0.006) values were found to be significantly higher in Crohn's patients than in healthy controls. Both FeNO and CalvNO correlated positively with the Crohn's Disease Activity Index. In conclusion, our results for FeNO and CalvNO confirm the presence of subclinical pulmonary involvement in Crohn's disease. eNO measurement may be of clinical value in the follow-up of Crohn's patients

The combined impact of exhaled nitric oxide and sputum eosinophils monitoring in asthma treatment: a prospective cohort study

BACKGROUND: Inhaled corticosteroids (ICS) treatment for asthma control is generally focused on lung function and symptoms, but inadequately correlated with airway inflammation. OBJECTIVE: To compare asthma control in a group of patients whose treatment was based on fraction of exhaled nitric oxide (FENO) and sputum eosinophils (intervention group) with a group in whom treatment was based on clinical score (control group). Study design and primary outcome: Randomized parallel-group longitudinal 24-month study including 5 visits every 6 months. A combination of asthma exacerbation rate and symptom score at 24 months was the primary outcome. PARTICIPANTS: Fourteen patients with eosinophilic asthma per group were included. RESULTS: In the intervention group, exacerbation rate/patient/year was reduced at 12 months (0.82) (-73%) and, to a greater extent at 24 months (0.5) (-84%) compared with baseline (3.21, p<0.01). In the control group, a significant reduction in exacerbation rate/patient/year was only observed between month 12 (3.0) and 24 (2.0, -33%, p<0.01). At 24 months, exacerbation rate was lower (-75%) in the intervention (0.5) than in the control group (2.0, p<0.05). Compared with baseline, mean symptom scores at 24 months were reduced in both groups (intervention group: -72%; control group: - 60%), but were lower in the intervention (8.1\ub11.0, p<0.05; -27%) than in the control group (11\ub12.6). ICS dose gradually increased in both groups throughout the study, with no between-group difference

Exhaled nitric oxide in patients with PiZZ phenotype-related alfa1-antitripsyn deficiency.

There is no report of exhaled NO (eNO) in subjects with different phenotypes of alpha1-anti-trypsin (AAT) deficiency. Exhaled nitric oxide was evaluated by means of single-breath chemiluminescence analysis (fractional exhaled concentration at the plateau level [plFE(NO)]) in 40 patients with AAT deficiency. Patients were divided according to the protease inhibitor (Pi) phenotype: PiMZ/MS, n = 25; PiSZ n = 6; PiZZ, n = 9. Nineteen healthy subjects served as controls. Levels of eNO in PiZZ patients were also compared with those of subjects, without AAT deficiency (PiMM), matched for diagnosis, sex, age, smoking habit and forced expiratory volume in 1 sec (FEV1). In AAT deficiency subjects airway hyper-responsiveness to methacholine (PD20 FEV1) was also assessed. plFE(NO) was significantly lower in the PiZZ group (4.5+/-1.4 ppb) than in matched PiMM subjects (8.2+/-3.8 ppb), in healthy controls (9.3+/-2.8 ppb) and in patients of other phenotypes. Dynamic lung volumes and DL(CO) were significantly lower in PiZZ than in other AAT-deficient patients. Bronchial hyper-responsiveness was not different among AAT phenotypes. These results suggest that eNO may be significantly reduced in PiZZ as compared to healthy control subjects and to AAT subjects with other phenotypes, independent of the level of airway obstruction. Whether, at least potentially, eNO may be considered as an early marker of lung involvement in AAT deficiency must be confirmed with studies on larger number of subjects