Barbara Vagaggini

Prognosis of occupational asthma

Several studies on the prognosis of occupational asthma have shown that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work. The determinants of this unfavourable prognosis of asthma are: long duration of exposure before the onset of asthma; long duration of symptoms before diagnosis; baseline airway obstruction; dual response after specific challenge test; and the persistence of markers of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsy. The relevance of immunological markers in the outcome of occupational asthma has not yet been assessed. Further occupational exposure in sensitized subjects leads to persistence and sometimes to progressive deterioration of asthma, irrespective of the reduction of exposure to the specific sensitizer, and only the use of particular protective devices effectively prevents the progression of the disease. A long-term follow-up study of toluene diisocyanate (TDI)-induced asthma showed that the improvement in bronchial hyperresponsiveness to methacholine occurred in a small percentage of subjects and only a long time after work cessation. Bronchial sensitivity to TDI may disappear, but non-specific bronchial hyperresponsiveness often persists unchanged, suggesting a permanent deregulation of airway tone. Steroid treatment significantly reduces nonspecific bronchial hyperresponsiveness only when started immediately after diagnosis.

Efficacy of standard rehabilitation in COPD outpatients with comorbidities.

A prospective study was performed to confirm the prevalence pattern of the most frequent co-morbidities and to evaluate whether characteristics of patients, specific comorbidities and increasing number of comorbidities are independently associated with poorer outcomes in a population with complex chronic obstructive pulmonary disease (COPD) submitted for pulmonary rehabilitation (PR). 316 outpatients (mean±sd age 68±7 yrs) were studied. The outcomes recorded were comorbidities and proportion of patients with a pre-defined minimally significant change in exercise tolerance (6-min walk distance (6MWD) +54 m), breathlessness (Medical Research Council (MRC) score -1 point) and quality of life (St George’s Respiratory Questionnaire -4 points). 62% of patients reported comorbidities; systemic hypertension (35%), dyslipidaemia (13%), diabetes (12%) and coronary disease (11%) were the most frequent. Of these patients, >45% improved over the minimum clinically important difference in all the outcomes. In a logistic regression model, baseline 6MWD (OR 0.99, 95% CI 0.98–0.99; p = 0.001), MRC score (OR 12.88, 95% CI 6.89–24.00; p = 0.001) and arterial carbon dioxide tension (OR 1.08, 95% CI 1.00–1.15; p = 0.034) correlated with the proportion of patients who improved 6MWD and MRC, respectively. Presence of osteoporosis reduced the success rate in 6MWD (OR 0.28, 95% CI 0.11–0.70; p = 0.006). A substantial prevalence of comorbidities in COPD outpatients referred for PR was confirmed. Only the individuals disability and the presence of osteoporosis were independently associated with poorer rehabilitation outcomes.

Comparison between hypertonic and isotonic saline-induced sputum in the evaluation of airway inflammation in subjects with moderate asthma

Background Hypertonic saline‐indueed sputum has recently been used for the evaluation of airway inflammation in asthma.

Malondialdehyde in Exhaled Breath Condensate as a Marker of Oxidative Stress in Different Pulmonary Diseases

Background. Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary oxidative stress biomarkers such as malondialdehyde (MDA). Subjects and Methods. We measured MDA levels in EBC in a large number of patients (N = 194) with respiratory diseases: asthma (N = 64), bronchiectasis (BE, N = 19), chronic obstructive pulmonary disease (COPD, N = 73), idiopathic pulmonary fibrosis (IPF, N = 38). Fourteen healthy nonsmoking subjects were included as controls. Results. Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV1% (rho:  −0.24, P < .05). Conclusions. EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV1 reduction.

Shuttle Walking Test and 6-Minute Walking Test Induce a Similar Cardiorespiratory Performance in Patients Recovering from an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Background: The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Objective: To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. Methods: We examined 18 patients (forced expiratory volume in 1 s: 48 ± 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. Results: Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (ρ: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. Conclusions: SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD.

Clinical predictors of the efficacy of a pulmonary rehabilitation programme in patients with COPD

OBJECTIVES To identify predictors of success for an 8week pulmonary rehabilitation programme (PRP) in patients with chronic obstructive pulmonary disease (COPD). METHODS Sixty patients were stratified in subgroups according to baseline findings: airway obstruction (FEV(1) >/= or <50% pred), pulmonary hyperinflation (TLC > or <or=120% pred), BMI value (BMI > or <or=25), cardiovascular (CV) comorbidity, and resting PaO(2) (PaO(2) >/= or <60mmHg). Outcome measurements of PRP were: >54m increase in 6min walking test (6MWT), or >4points reduction in total score of S. George Respiratory Questionnaire (SGRQ). Logistic regression analysis was used. RESULTS After PRP there was a significant improvement in exercise tolerance and quality of life, which correlated with baseline FEV(1)/VC, PaO(2), SpO(2), 6MWT and SGRQ. SGRQ significantly decreased and 6MWT significantly increased after PRP in all subgroups, except for patients with CV comorbidities. Both univariate and multivariate logistic regression analyses showed that BMI>25 and resting PaO(2)<60mmHg were independent predictors of PRP efficacy in terms of improvement of 6MWT, but not of SGRQ scores. CONCLUSIONS Clinical and functional baseline findings do not predict the response to PRP in COPD. The greater efficacy in patients with BMI>25 or with PaO(2)<60mmHg may be due to a greater deconditioning in overweight patients, and to a larger room for improvement in hypoxemic patients.

Induced sputum is a reproducible method to assess airway inflammation in asthma

To evaluate the reproducibility of induced sputum analysis, and to estimate the sample size required to obtained reliable results, sputum was induced by hypertonic saline inhalation in 29 asthmatic subjects on two different days. The whole sample method was used for analysis, and inflammatory cells were counted on cytospin slides. Reproducibility, expressed by intra-class correlation coefficients, was good for macrophages (+0.80), neutrophils (+0.85), and eosinophils (+0.87), but not for lymphocytes (+0.15). Detectable differences were 5.5% for macrophages, 0.6% for lymphocytes, 5.2% for neutrophils, and 3.0% for eosinophils. We conclude that analysis of induced sputum is a reproducible method to study airway inflammation in asthma. Sample sizes greater than ours give little improvement in the detectable difference of eosinophil percentages.

Asthma Control Test (ACT): Comparison with Clinical, Functional, and Biological Markers of Asthma Control.

Background. Asthma Control Test (ACT) is a simple tool for assessing the level of asthma control in clinical practice, and it has been validated in comparison with a general clinical assessment of asthma control, including forced expiratory volume in the first second (FEV1). Objective. To evaluate the relationship between ACT score and clinical and functional findings of asthma control and biomarkers of airway inflammation. Methods. A total of 68 asthmatic patients observed in our asthma clinic (33 regularly treated with inhaled corticosteroids (ICS) and 35 ICS-naïve) filled ACT questionnaire and underwent the following measurements: (a) FEV1 before and after salbutamol; (b) exhaled nitric oxide; (c) bronchial hyperresponsiveness to methacholine; (d) sputum eosinophil count; and (e) daytime and nighttime symptoms, rescue salbutamol, and twice-daily peak expiratory flow (PEF) recording on a 4-week diary card. Results. ACT score significantly correlated with symptom score, rescue medication use, and PEF variability, but not with FEV1, FEV1 reversibility, and markers of airway inflammation, which could not distinguish controlled from uncontrolled patients according to ACT, regardless of ICS treatment. Conclusion. ACT score is a valid tool to simply assess the current level of asthma control in terms of symptoms, rescue medication use, and PEF variability. Pulmonary function and biomarkers of airway inflammation are not related to the clinical asthma control as assessed by ACT and may represent additional measurements potentially useful in asthma management.

Comparison Between Peak Expiratory Flow and Forced Expiratory Volume in One Second (FEV1) During Bronchoconstriction Induced by Different Stimuli

To evaluate the sensitivity of peak expiratory flow (PEF), obtained by portable peak flow meter, in detecting mild changes in airway caliber as assessed by forced expiratory volume in 1 sec (FEV1), we studied 184 subjects who underwent different bronchial challenge tests for suspected bronchial asthma. We measured FEV1 and PEF during bronchoconstriction induced by different stimuli: allergen, methacholine, toluene diisocyanate vapors, exercise, or distilled water inhalation; a total of 186 tests were examined. Before and at different times after challenge, FEV1 was measured, and immediately after, PEF was obtained by Mini-Wright or Assess Peak Flow Meter; each time FEV1 and PEF were taken as the best of three satisfactory tracings. The median FEV1 change from baseline value of all steps in the different challenge tests was 7.5% (range: 0-66%). The correlation coefficients between FEV1 and PEF percent changes in different challenge tests were low (Spearmans p: 0.27-0.69), with high scattering of the data. The concordance between classes of percent changes in FEV1 and PEF was also low (Cohens weighted kappa: 0.28-0.42). In subjects with a FEV1 fall > 15% after challenge, the median PEF change after bronchoconstriction was lower than the corresponding FEV1 change [17% (0-52) vs. 27% (17-66)]. When different cutoff limits of PEF percent change were considered, the sensitivity of PEF to detect a significant change in FEV1 (15 or 20% change) during bronchoconstriction was low; specificity was in general higher than sensitivity. We conclude that PEF and FEV1 changes are poorly related during mild bronchoconstriction induced by different stimuli. The low sensitivity of PEF to detect mild changes in airway caliber may represent a limit in the use of PEF in the day-to-day monitoring of asthma.

Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD subjects

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermittent exercise, on different days and in random order. Before and 2 h after exposure, symptom score and results of pulmonary function tests (PFTs) were assessed. All subjects performed nasal lavage and hypertonic saline (HS) inhalation to collect sputum 2 h after both exposures. Asthmatic subjects had a higher percentage of eosinophils than normal and COPD subjects in HS-induced sputum after air (asthmatics: median 13 (range 0.4-37)%; normals: 0 (range 0-2)%; COPD 1.8 (range 0.1-19)%), whilst COPD patients showed a higher percentage of neutrophils than the two others groups. No significant differences in PFT values or percentages of inflammatory cells were observed in nasal lavage and in HS-induced sputum in normal, asthmatic and COPD subjects after NO2 exposure compared to air exposure, except for a mild decrease in forced expiratory volume in one second (FEV1) 2 h after NO2 exposure in COPD patients. Symptom score showed a mild increase after NO2 exposure both in normal subjects and in COPD patients. We conclude that short-term exposure to 0.3 ppm nitrogen dioxide does not induce an early detectable acute inflammation in proximal airways of normal subjects or of patients with asthma or chronic obstructive pulmonary disease.