Small airway dysfunction is associated to excessive bronchoconstriction in asthmatic patients.

BACKGROUND: We investigated whether a relationship between small airways dysfunction and bronchial hyperresponsiveness (BHR), expressed both in terms of ease of airway narrowing and of excessive bronchoconstriction, could be demonstrated in asthma. METHODS: 63 (36 F; mean age 42 yr ± 14) stable, mild-to-moderate asthmatic patients (FEV1 92% pred ±14; FEV1/FVC 75% ± 8) underwent the methacholine challenge test (MCT). The degree of BHR was expressed as PD20 (in µg) and as ∆FVC%. Peripheral airway resistance was measured pre- and post-MCT by impulse oscillometry system (IOS) and expressed as R5-R20 (in kPa sL-1). RESULTS: All patients showed BHR to methacholine (PD20 < 1600 µg) with a PD20 geometric (95% CI) mean value of 181(132-249) µg and a ∆FVC% mean value of 13.6% ± 5.1, ranging 2.5 to 29.5%. 30 out of 63 patients had R5-R20 > 0.03 kPa sL-1 (>upper normal limit) and showed ∆FVC%, but not PD20 values significantly different from the 33 patients who had R5-R20 ≤ 0.03 kPa sL-1 (15.8% ± 4.6 vs 11.5% ± 4.8, p < 0.01 and 156(96-254) µg vs 207 (134-322) µg, p = 0.382). In addition, ∆FVC% values were significantly related to the corresponding pre- (r = 0.451, p < 0.001) and post-MCT (r = 0.376, p < 0.01) R5-R20 values. CONCLUSIONS: Our results show that in asthmatic patients, small airway dysfunction, as assessed by IOS, is strictly associated to BHR, expressed as excessive bronchoconstriction, but not as ease of airway narrowing.

Decreased maturation of dendritic cells in the central airways of COPD patients is associated with VEGF, TGF-ß and vascularity.

BACKGROUND: Dendritic cells (DCs) have a pivotal role in the onset and regulation of innate and adaptive immune responses. Moreover, DCs can interact with angiogenic modulators, resulting in modification of their biology and participation in angiogenesis. OBJECTIVES: This study was designed to evaluate the relationship between the density of DCs, vascularity and expression of angiogenic factors [vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß and basic fibroblast growth factor (bFGF)] in the central airways of chronic obstructive pulmonary disease (COPD) patients. METHODS: The study included 20 patients with moderate/severe COPD and 8 healthy control subjects. Bronchial biopsies were evaluated by immunohistochemistry. Specimens were examined for CD83 and CD207 to mark mature and immature DCs, respectively, for collagen IV to evaluate vascularity, and for VEGF, TGF-ß and bFGF. RESULTS: Compared to controls, COPD patients had a significant reduction of CD83+ cells and an increased CD207/CD83 ratio (p < 0.05). Vascularity, VEGF, TGF-ß and bFGF were also significantly increased in COPD patients as compared to controls (p < 0.01). In COPD patients, CD83+ cells were inversely related to VEGF and TGF-ß expression (p < 0.05). Moreover, the CD207/CD83 ratio was positively related to VEGF, TGF-ß and vascularity (p < 0.05). Finally, CD207+ cells were inversely related to FEV1 (p < 0.05). CONCLUSION: Our results show a reduced maturation of DCs in COPD that was related to airway vascularity and angiogenic factors (VEGF and TGF-ß). Additionally, immature DCs were significantly related to disease severity. We propose that the interplay between airway vascular changes, on one hand, and DCs maturation on the other, may play a key role in the pathogenetic mechanisms of COPD.

Small airway dysfunction by impulse oscillometry in asthmatic patients with normal forced expiratory volume in the 1st second values.

Small airways are relevant to the pathophysiology of asthma. We investigated whether in asthmatic patients with normal forced expiratory volume in the 1st second (FEV(1)) values, impulse oscillometry system (IOS), as a measure of small airway function, contributed additional information to spirometry either at baseline or after bronchodilator, and whether it was related to the disease control. The fall in resistance from 5 to 20 Hz (R5-R20) and reactance at 5 Hz (X5) by IOS and spirometry measures of small airway function (forced expiratory flow at 25-75% [FEF(25-75)] and forced vital capacity/slow inspiratory vital capacity [FVC/SVC]) at baseline and after 400 micrograms of salbutamol were prospectively measured in 33 asthmatic patients (18 women; age range, 18-66 years). Disease control was assessed by the Asthma Control Test (ACT). R5-R20 but not X5 values were significantly related to FEF(25-75) and FVC/SVC values (p < 0.05 for both correlations). When the bronchodilator response was assessed, no correlation was found among IOS and spirometry changes. ACT scores were related to R5-R20, FEF(25-75), and FVC/SVC values (p < 0.01 for all correlations). In asthmatic patients with normal FEV(1) values, R5-R20 values were related to spirometry measures of small airway function. However, when the bronchodilator response was assessed, IOS and spirometry provided quite different results. Moreover, small airway dysfunction, as assessed by IOS and spirometry, was associated with poor disease control and history of asthma exacerbations. The results of this study confirm the value of IOS, as an investigative tool, and suggest that in asthmatic patients with normal FEV(1) values and poor disease control, small airway function should be investigated.

Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial.

BACKGROUND: Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting ß2 agonist combination therapy. METHODS: This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 µg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 µg fluticasone/salmeterol Diskus daily or 400/24 µg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency. RESULTS: Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events. CONCLUSIONS: Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 µg fluticasone/salmeterol daily or 400/24 µg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control. TRIAL REGISTRATION: clinicaltrials.gov NCT00497237.

Overweight is associated with airflow obstruction and poor disease control but not with exhaled nitric oxide change in an asthmatic population.

BACKGROUND: The role of an elevated body mass index (BMI) in asthma remains controversial. OBJECTIVES: To investigate the relationship between overweight (BMI >25 and ≤30), lung function, disease control, and airway inflammation in an asthmatic population. METHODS: We consecutively studied 348 patients (age 43 ± 16 years; 211 females). In all patients, BMI, spirometry, the Asthma Control Test (ACT), and fractional exhaled nitric oxide (FeNO; ppb) were measured. RESULTS: One hundred forty-five patients were overweight and, as compared to those with normal BMI, had lower values of FVC, FEV(1), and FEV(1)/FVC and of FEF(25-75) even when normalized for FVC (p < 0.05 for each comparison). The ratio between the number of patients with well-controlled asthma (ACT ≥20) and that of patients with poorly controlled asthma (ACT < 20) was significantly lower in overweight patients (1.07 vs. 1.84; χ(2) = 6.030, p < 0.01). In overweight patients, the odds ratio of uncontrolled asthma expressed by logistic regression analysis was 1.632 (95% CI = 1.043-2.553), independently of gender, atopy, smoking habit, and inhaled steroid therapy. No difference was observed in FeNO values between overweight and normal weight patients (27.7 ± 2.3 vs. 27.9 ± 2.2 ppb). CONCLUSIONS: Our results show that, in an asthmatic population, overweight is associated with airflow obstruction and poor disease control but not with FeNO change. The findings of the present study support the view that other factors besides airway inflammation alone may explain the relationship between asthma and an elevated BMI.

Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients.

BACKGROUND: Pulmonary hyperinflation has the potential for significant adverse effects on cardiovascular function in COPD. The aim of this study was to investigate the relationship between dynamic hyperinflation and cardiovascular response to maximal exercise in COPD patients. METHODS: We studied 48 patients (16F; age 68 yrs ± 8; BMI 26 ± 4) with COPD. All patients performed spirometry, plethysmography, lung diffusion capacity for carbon monoxide (TLco) measurement, and symptom-limited cardiopulmonary exercise test (CPET). The end-expiratory lung volume (EELV) was evaluated during the CPET. Cardiovascular response was assessed by change during exercise in oxygen pulse (ΔO2Pulse) and double product, i.e. the product of systolic blood pressure and heart rate (DP reserve), and by the oxygen uptake efficiency slope (OUES), i.e. the relation between oxygen uptake and ventilation. RESULTS: Patients with a peak exercise EELV (%TLC) ≥ 75% had a significantly lower resting FEV1/VC, FEF50/FIF50 ratio and IC/TLC ratio, when compared to patients with a peak exercise EELV (%TLC) < 75%. Dynamic hyperinflation was strictly associated to a poor cardiovascular response to exercise: EELV (%TLC) showed a negative correlation with ΔO2Pulse (r = - 0.476, p = 0.001), OUES (r = - 0.452, p = 0.001) and DP reserve (r = - 0.425, p = 0.004). Furthermore, according to the ROC curve method, ΔO2Pulse and DP reserve cut-off points which maximized sensitivity and specificity, with respect to a EELV (% TLC) value ≥ 75% as a threshold value, were ≤ 5.5 mL/bpm (0.640 sensitivity and 0.696 specificity) and ≤ 10,000 Hg · bpm (0.720 sensitivity and 0.783 specificity), respectively. CONCLUSION: The present study shows that COPD patients with dynamic hyperinflation have a poor cardiovascular response to exercise. This finding supports the view that in COPD patients, dynamic hyperinflation may affect exercise performance not only by affecting ventilation, but also cardiac function.

Understanding patients with asthma and COPD: insights from a European study.

AIMS: To understand the needs of people with asthma and COPD, and to identify opportunities for improved care. METHODS: Quantitative questionnaire-based survey performed in five European countries on patients with asthma and COPD. Questionnaires were administered to patients using Computer Assisted Web Interview methodology. RESULTS: 1022 patients with asthma (UK [n=190]; Germany [n=214]; France [n=200]; Italy [n=222]; Spain [n=196]) and 719 patients with COPD (UK [n=153]; Germany [n=147]; France [n=145]; Italy [n=140]; Spain [n=134]) were enrolled in the study. 32% of those with asthma and 67% of those with COPD considered that their condition had a significant effect on their quality of life, and stigma and emotional distress was common. Many expressed concern regarding potential medication side effects or that medicines might lose their effect with time. Major discrepancies between expectations and patient satisfaction with the doctor-patient relationship were observed, including a need to be consulted in the choice of inhalers. Consultations were infrequent, and 75% of respondents sought additional information beyond that received during consultations - commonly from the internet. CONCLUSIONS: Patient satisfaction was high but information needs were not addressed and the emotional burden of disease is underappreciated.

Patient assessment and prevention of pulmonary side-effects in surgery.

PURPOSE: The review deals with the clinical and functional assessment that is requested before surgical operations and with the pulmonary effects of surgery. Moreover, an evidence-based approach to prevent postoperative pulmonary complications is provided. RECENT FINDINGS: Spirometry is recommended for patients with a history of tobacco use or dyspnoea who are considered for cardiac or upper abdominal surgery and for all patients who are candidates for lung resection. For patients undergoing lung resection, low complication rates have been associated with a preoperative forced expiratory volume at first second value of at least 2 litres or 80% of the predicted value and at least 1.5 litres or 60% of the predicted value in the case of pneumonectomy or lobectomy, respectively. At-risk patients are recommended to undergo split lung function studies to estimate the residual parenchyma function after surgery. In patients with borderline estimated values, a cardiopulmonary exercise test is recommended to stratify further risk. Preventive interventions of postoperative pulmonary complications, including pain control, respiratory chest physiotherapy and continuous positive airway pressure may effectively reduce the occurrence of pulmonary complications. SUMMARY: Pulmonary functional assessment is relevant in patients candidates for surgery. The prevention of the postoperative pulmonary complications is one of the most important goals of the treatment of patients undergoing surgery.

Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma.

BACKGROUND: Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma. We investigated whether the symptom-driven use of a combination of beclomethasone dipropionate and albuterol (also known as salbutamol) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol. METHODS: We conducted a 6-month, double-blind, double-dummy, randomized, parallel-group trial. After a 4-week run-in, patients with mild asthma were randomly assigned to receive one of four inhaled treatments: placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed (as-needed combination therapy); placebo twice daily plus 100 microg of albuterol as needed (as-needed albuterol therapy); 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed (regular beclomethasone therapy); or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed (regular combination therapy). The primary outcome was the morning peak expiratory flow rate. RESULTS: In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters (88.36% of the predicted value), the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher (P=0.04) and the number of exacerbations during the 6-month treatment was lower (P=0.002) in the as-needed combination therapy group than in the as-needed albuterol therapy group, but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy. The cumulative dose of inhaled beclomethasone was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy (P<0.001 for both comparisons). CONCLUSIONS: In patients with mild asthma, the symptom-driven use of inhaled beclomethasone (250 microg) and albuterol (100 microg) in a single inhaler is as effective as regular use of inhaled beclomethasone (250 microg twice daily) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid. (ClinicalTrials.gov number, NCT00382889 [ClinicalTrials.gov].).

The role of the bronchial microvasculature in the airway remodelling in asthma and COPD.

In recent years, there has been increased interest in the vascular component of airway remodelling in chronic bronchial inflammation, such as asthma and COPD, and in its role in the progression of disease. In particular, the bronchial mucosa in asthmatics is more vascularised, showing a higher number and dimension of vessels and vascular area. Recently, insight has been obtained regarding the pivotal role of vascular endothelial growth factor (VEGF) in promoting vascular remodelling and angiogenesis. Many studies, conducted on biopsies, induced sputum or BAL, have shown the involvement of VEGF and its receptors in the vascular remodelling processes. Presumably, the vascular component of airway remodelling is a complex multi-step phenomenon involving several mediators. Among the common asthma and COPD medications, only inhaled corticosteroids have demonstrated a real ability to reverse all aspects of vascular remodelling. The aim of this review was to analyze the morphological aspects of the vascular component of airway remodelling and the possible mechanisms involved in asthma and COPD. We also focused on the functional and therapeutic implications of the bronchial microvascular changes in asthma and COPD.

Measurement of fractional exhaled nitric oxide by a new portable device: comparison with the standard technique.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) measurement is a reliable, noninvasive marker of airway inflammation. The use of portable FeNO analyzers may enable the assessment of airway inflammation in primary care. OBJECTIVE: The authors compared FeNO values obtained by a new portable device (NObreath, Bedfont, UK) to those of the standard stationary analyzer (NIOX, Aerocrine, Sweden) in a large cohort of asthmatic patients. METHODS: One hundred and fifty-four (age range: 14-83 years, forced expiratory volume in one second [FEV(1)] range: 48-134% predicted, asthma control test [ACT] range: 7-25) out of 168 recruited patients completed the study. Each patient performed at least two valid FeNO measurements at a constant flow rate of 50 ml/s on each of the two analyzers. RESULTS: A significant relationship between the FeNO values obtained by the two devices (r = .95, p < .001) was found. Altman-Bland plot confirmed this agreement. Within-patient repeatability was excellent in both devices. Intraclass correlation coefficients for NIOX and NObreath values were .925 and .967, respectively. By means of receiver operating characteristic curve analysis, the FeNO cutoff points that better identified patients with ACT ≥ 20 were 15 ppb (0.84 sensitivity and 0.42 specificity) by NIOX and 25 ppb (0.53 sensitivity and 0.69 specificity) by NObreath. Easiness to use of both devices, assessed by visual analogue scale was not different. CONCLUSION: FeNO measurements obtained by the new portable FeNO analyzer are reliable because they are directly comparable with those obtained by the stationary standard device. The use of portable instruments may facilitate the FeNO measurement in primary care.

Flying with respiratory disease.

Patients with respiratory diseases may be at risk during flight because at cruising altitude an important hypobaric hypoxia may occur. The only absolute contraindications to flying in these patients are pneumothorax, bronchogenic cyst and severe pulmonary hypertension. In order to evaluate the risks related to air travel in patients with respiratory diseases, an evaluation of their fitness to fly, including the hypoxia altitude simulation test, is required. The fitness to fly evaluation can identify patients requiring supplemental oxygen during flight which is provided by most airlines when prescribed by the passenger's physician. This review deals with the cardiorespiratory effects of flight, the risks associated with respiratory diseases during air travel and the procedures to follow in order to assess fitness to fly in patients with respiratory disorders.

Is the use of beta-blockers in COPD still an unresolved dilemma?

Beta-blockers are competitive antagonists at beta-adrenergic receptors (beta-AR) and are a life-saving form of treatment in different cardiovascular diseases (CVD). Despite current guidelines supporting the use of selective beta(1)-blockers in patients with CVD and especially in heart failure (HF), they are still largely underused, mostly as a consequence of the presence of chronic obstructive pulmonary disease (COPD). In primary care, prevalence of COPD in patients with HF is approximately 25%, and it will rise in the next years. In the general population, only 20% of COPD patients with HF are treated with beta-blockers. beta-Blockers may result in pulmonary adverse effects that are relevant to COPD patients. Bronchoconstriction may be the consequence of: absence of cardioselectivity; loss of cardioselectivity at high doses, and unopposed stimulation of cholinergic muscarinic M(2) receptors. The concern of inducing bronchospasm is the more likely explanation of a poor prescription of beta-blockers in patients with CVD also suffering from COPD. However, under carefully controlled conditions, which include close monitoring of lung function and appropriate selection of the drug and titration of the dose on a case-by-case basis, selective beta(1)-blockers can be safely administered to most patients with COPD. Pneumologists and cardiologists should develop a detailed and standardized protocol to guide the use of selective beta(1)-blockers in everyday practice, which could significantly reduce the physicians' mistrust of beta-blockers in COPD patients.

Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis.

BACKGROUND: Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. OBJECTIVES: The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO). METHODS: Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 +/- 13 years, body mass index of 25 +/- 5 kg/m2). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.The data are given as mean values +/- SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant. RESULTS: Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 +/- 8 mmHg), whereas right ventricular function was normal (TAPSE 23 +/- 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01). CONCLUSIONS: Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.

Both bronchial and alveolar exhaled nitric oxide are reduced with extrafine beclomethasone dipropionate in asthma.

Exhaled nitric oxide (NO) is a noninvasive marker of airway inflammation. Beclomethasone dipropionate (BDP) is the only inhaled corticosteroid (ICS) available as both extrafine and nonextrafine hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation. The present study was designed to evaluate whether the different patterns of lung deposition of two HFA BDP formulations are associated with a different effect on bronchial and alveolar NO. This was a prospective double-blind, randomized, controlled, crossover study. After a 2-week placebo run-in period without ICSs, asthmatic patients were randomized to extrafine BDP, 100 µg, b.i.d. or nonextrafine BDP, 250 µg, b.i.d. for two 2-week periods separated by a 2-week washout period. Fourteen patients (5 men) with a mean age 37 years and mean baseline forced expiratory volume in 1 second (FEV1) of 83% of predicted were analyzed. Exhaled bronchial NO was significantly (p < 0.001) reduced in both treatment groups when compared with the last week of run-in period, whereas alveolar NO was significantly (p < 0.001) reduced only with extrafine BDP. Moreover, extrafine BDP was superior to nonextrafine BDP in both parameters (p < 0.05). Extrafine but not nonextrafine BDP HFA formulation lowers both bronchial and alveolar exhaled NO in asthmatic patients. ICS distribution throughout the whole bronchial tree could be important in patients who do not gain optimal control of inflammation with conventional nonextrafine ICS.

Respiratory function in subjects with chronic obstructive pulmonary disease (COPD) and atmospheric pollution in the city of Parma. Preliminary analysis.

A hospital case record study was carried out enlisting urgently hospitalized subjects for chronic obstructive pulmonary disease (COPD) in order to study the percentage values variations of Vital Capacity (VC), Forced Vital Capacity (FVC) and maximum expiratory volume in 1 second (FEV1) based on atmospheric pollution trend in Parma city evaluated by PM10, NO2 and O3 concentrations. The results showed an association only between PM10 and hospitalizations for COPD with statistically significant differences between PM10 concentrations assessed 3-4 days before hospitalizations of the study subjects and the ones established in the days without any hospitalization. The regression analysis between PM10 and respiratory function concerning PM10 concentration at 24, 48, 72, 96 hours before the hospitalization showed significant association between FVC% and FEV1% and PM10 concentrations at 96 hours. The calculated odd ratio resulted equal to 1016 (L.C. 1001-1032) which corresponds to an increase of hospitalization probability for COPD equal to 1.6% for PM10 increment unit.

The walking capacity assessment in the respiratory patient.

Exercise testing is commonly used in respiratory patients to assess their degree of disability, prognosis for survival, presence of exercise-induced hypoxemia and response to treatment. Recently, simple exercise tests, which are based on walking, have been developed and are increasingly being used both for clinical and research purposes. The 6-min walk test (6-MWT) is the most widely used and simply consists in the measurement of the distance walked in 6 min. The 6-MWT is self-paced and differs from the shuttle walking test, which is externally paced via a recorded metronome and entails incrementally faster speeds. Although the field walking tests do not require complex equipment, they can provide reliable and useful clinical information. This review deals with the validity, reliability and interpretation of these walking tests in the assessment of patients with chronic respiratory disease.

Safety and tolerability of ribosome-component immune modulator in adults and children.

Ribosomal preparations (ribosome-component immune modulators [RCIMs]) do not contain attenuated bacteria and, in contrast to live bacterial extracts, which may induce severe side effects, retain immune stimulating activity without infectious capability. This study was designed to profile the tolerability of RCIM by reviewing narratively all randomized, double-blind, placebo-controlled clinical trials and open-label studies as well as data from postmarketing surveillance studies representing >30 million prescriptions. In the various clinical trials, RCIM tolerability in terms of clinical and laboratory parameters was good. There were no significant differences between patients receiving active treatment or placebo in a survey of tolerability results from randomized, double-blind, placebo-controlled studies. Pharmacovigilance analysis does not show a change in the risk profile of RCIM. The only contraindication was correlated with known hypersensitivity to any of the product components. RCIM should not be used in case of acute streptococcal glomerulonephritis, acquired immune deficiency syndrome, severe viral disease, or severe autoimmune disease. Risk associated with the use of RCIM is negligible in recurrent upper and lower airway infections in selected populations, such as children and elderly people.

Cost effective analysis of ribosome-component immune modulation.

In childhood, recurrent airway infections are the most common cause for medical visits and hospitalizations. Their economic impact is considerable and their treatment accounts for a substantial quota of the health care budget. Despite documented efficacy and safety, ribosomal bacterial vaccine and membrane fraction use is still limited by being prevalently considered for prevention rather than treatment. The objective of this study was to analyze the economic benefit achieved with ribosomal immunotherapy. A review was performed of available literature data on economic parameters. Pharmacoeconomic studies published during the past few years showed how the use of ribosome component immune modulator is capable of reducing expenditure associated with treatment of recurrent respiratory infection and allows achievement of substantial savings in terms of cost, time, and loss of productivity. The initial cost of prevention in patients suffering from chronic respiratory infections is offset by a subsequent saving arising from less recurrence of disease. Direct management costs such as therapy courses, medical visits, medical exams, hospitalizations, etc., and indirect costs such as absence from school and work are not routinely considered by primary care physicians.