Airway inflammatory profile is correlated with symptoms in stable COPD: A longitudinal proof-of-concept cohort study.

BACKGROUND AND OBJECTIVE: Symptoms negatively impact the quality of life and long-term prognosis of patients with chronic obstructive pulmonary disease (COPD). Little is known about the relationship linking airway inflammation and symptoms in stable COPD. In this study, we evaluated whether respiratory symptoms in COPD are related to sputum inflammatory cellular profile and whether symptom changes are associated with changes in airway inflammation. METHODS: A total of 40 patients with stable COPD with moderate-to-severe airflow obstruction were enrolled. Patients were visited weekly over 4 weeks. At each visit, patients underwent clinical assessments, lung function tests and sputum induction. Patients recorded daily dyspnoea, sputum and cough scores. RESULTS: The changes between two consecutive visits in the percent of sputum neutrophils and eosinophils were related to the changes in the cough (P < 0.001; r = 0.63) and dyspnoea scores (P < 0.001; r = 0.58) of the prior week. Furthermore, using regression analyses, we were able to demonstrate that changes in the cough score were specifically associated to the change in neutrophils, while changes in the dyspnoea score and use of rescue medications were associated with changes in eosinophils numbers. CONCLUSION: Our study showed an association between symptoms and the sputum inflammatory profile. In particular, changes in symptoms (cough and dyspnoea) were correlated with changes in the specific sputum inflammatory cell components of airway inflammation (neutrophils and eosinophils, respectively), providing novel information on the mechanisms of disease manifestation.

Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD.

Inhaled corticosteroid-containing medications reduce the frequency of COPD exacerbations (mainly infectious in origin) while paradoxically increasing the risk of other respiratory infections. The aim was to determine the effects of inhaled corticosteroids on airway microbial load in COPD patients and evaluate the influence of the underlying inflammatory profile on airway colonisation and microbiome.This is a proof-of-concept prospective, randomised, open-label, blinded endpoint study. Sixty patients with stable moderate COPD were randomised to receive one inhalation twice daily of either a combination of salmeterol 50 µg plus fluticasone propionate 500 µg or salmeterol 50 µg for 12 months. The primary outcome was the change of sputum bacterial loads over the course of treatment.Compared with salmeterol, 1-year treatment with salmeterol plus fluticasone was associated with a significant increase in sputum bacterial load (p=0.005), modification of sputum microbial composition and increased airway load of potentially pathogenic bacteria. The increased bacterial load was observed only in inhaled corticosteroid-treated patients with lower baseline sputum or blood eosinophil (≤2%) levels but not in patients with higher baseline eosinophils.Long-term inhaled corticosteroid treatment affects bacterial load in stable COPD. Lower eosinophil counts are associated with increased airway bacterial load.

Midazolam in flexible bronchoscopy premedication: effects on patient-related and procedure-related outcomes.

BACKGROUND: The role of midazolam in flexible bronchoscopy premedication has been debated. The aim of the present study was to evaluate whether midazolam premedication increases the patient-reported tolerance and the physician-reported or nurse-reported feasibility of bronchoscopy. METHODS: Randomized, double-blinded, placebo-controlled, 3-arm study. The study population included patients undergoing bronchoscopy for appropriate clinical indications. Patients were randomly assigned to receive 0.035 mg/kg intravenous midazolam (low dose), 0.07 mg/kg (high dose), or placebo. Vital parameters were monitored in continuum during the procedure. At the end of the procedure, the operating physician and assisting nurse filled out a questionnaire to score the procedure-related outcomes (satisfaction, feasibility, completeness, and unexpected events). Patients were asked to fill out a specific questionnaire to assess the patient-reported tolerance and satisfaction 2 hours after the bronchoscopy. RESULTS: A total of 100 patients (mean age 58.6±1.0; 57% male) were included in the study (33 in the low-dose midazolam group, 34 in the high-dose midazolam group, and 33 in the placebo group). The patient-reported tolerance score was significantly higher in the high-dose midazolam group than in the placebo group (P<0.01). No differences were found in the 3 groups in terms of the physician-reported feasibility and completeness of the procedure. In the groups of patients premedicated with midazolam, significant oxygen desaturation was recorded (at 10 and 8 min after the introduction of the bronchoscope) compared with the baseline value (P<0.01). CONCLUSIONS: In our study, premedication with midazolam increased the patient-reported tolerance of the bronchoscopy. However, the absence of premedication did not affect the diagnostic yield of the procedure.

Reducing agents decrease the oxidative burst and improve clinical outcomes in COPD patients: a randomised controlled trial on the effects of sulphurous thermal water inhalation.

BACKGROUND: Inhalation of thermal water with antioxidant properties is empirically used for COPD. AIMS: To evaluate the effects of sulphurous thermal water (reducing agents) on airway oxidant stress and clinical outcomes in COPD. METHODS: Forty moderate-to-severe COPD patients were randomly assigned to receive 12-day inhalation with sulphurous thermal water or isotonic saline. Patients were assessed for superoxide anion (O2 (-)) production in the exhaled breath condensate and clinical outcomes at recruitment, the day after the conclusion of the 12-day inhalation treatment, and one month after the end of the inhalation treatment. RESULTS: Inhalation of reducing agents resulted in a significant reduction of O2 (-) production in exhaled breath condensate of COPD patients at the end of the inhalatory treatment and at followup compared to baseline. A significant improvement in the COPD assessment test (CAT) questionnaire was shown one month after the end of the inhalatory treatment only in patients receiving sulphurous water. CONCLUSION: Thermal water inhalation produced an in vivo antioxidant effect and improvement in health status in COPD patients. Larger studies are required in order to evaluate whether inhalation of thermal water is able to modify relevant clinical outcomes of the disease (the study was registered at clinicaltrial.gov-identifier: NCT01664767).