Alpha-1 antitrypsin deficiency is significantly associated with atopy in asthmatic patients.

Background: Although the etiology and disease mechanisms of asthma and alpha-1 antitrypsin deficiency (AATD) are distinct, several reports indicate that asthma is common in AATD patients, however the relationships between asthma and AATD are poorly described in the literature.Objectives: The aim of the study was to investigate in a cohort of outpatients affected by mild to moderate asthma the clinical features that may differentiate asthmatic patients with and without mutation on SERPINA1 gene.Methods: Seven hundred thirty-five asthmatic outpatients underwent quantitative analysis of the serum level of alpha-1antitrypsin. According to the literature only sixty-seven out of seven hundred thirty-five asthmatic patients were submitted to genetic analysis to identify AATD and non-AATD subjects. Fifty-eight patients were studied. Clinical and functional data, including lung function, atopy and bronchial hyperactivity, were recorded.Results: The fifty-eight asthmatic patients were divided in AATD patients (n = 22) and non AATD patients (n = 36), according to genotype. The presence of atopy was significantly higher in patients with AATD than in those without AATD (91% vs. 64%; p = 0.031). AATD patients reported allergic manifestations more than non AATD patients (77% vs. 47%; p = 0.030).Conclusion: Our study shows that the presence of atopy in asthmatic patients with AATD is significantly higher than in asthmatic patients without gene mutation. In addition, a higher percentage of AATD patients self-reported allergic manifestations. No significant differences in respiratory symptoms, physical examination, disease severity or inflammation markers were found between AATD patients and non AATD patients.

The COPD assessment test and the modified Medical Research Council scale are not equivalent when related to the maximal exercise capacity in COPD patients.

INTRODUCTION: The management and treatment of Chronic Obstructive Pulmonary Disease (COPD) are based on a cutoff point either of ≥ 10 on the COPD Assessment Test (CAT) or of ≥ 2 of the Medical Research Council (mMRC). Up to now, no study has assessed the equivalence between CAT and mMRC, as related to exercise tolerance in COPD. The aim of this study was to investigate as primary outcome the relationship between CAT and mMRC and maximal exercise capacity in COPD patients. We also evaluated as secondary outcome the agreement between CAT (≥ 10) and mMRC (≥ 2) to categorize patients according to their exercise tolerance. MATERIAL AND METHODS: 118 consecutive COPD patients (39 females), aged between 47 and 85 years with a wide range of airflow obstruction and lung hyperinflation were studied. Maximal exercise capacity was assessed by cardiopulmonary exercise test. RESULTS: CAT and mMRC scores were significantly related to VO2 peak (p<0.01). CAT (≥ 10) and mMRC (≥ 2) have a high likelihood to be associated to a value of VO2 peak less than 15.7 and 15.6 mL/kg/min, respectively. The interrater agreement between CAT (≥ 10) and mMRC (≥ 2) was found to be fair (κ = 0.20) in all patients but slight when they were subdivided in those with VO2 peak < 15 mL/kg/min and in those with VO2 peak ≥ 15 mL/kg/min (κ = 0.10 and κ = 0.20 respectively). CONCLUSION: This study shows that CAT and mMRC are useful tools to predict exercise tolerance in COPD, but they cannot be considered as supplementary measures.

Follow-up in pulmonary sarcoidosis: comparison between HRCT and pulmonary function tests.

PURPOSE: The authors assessed the clinical usefulness of high-resolution computed tomography (HRCT) for monitoring sarcoidosis by comparing changes on HRCT with those on pulmonary function test (PFT) results over time. MATERIALS AND METHODS: The baseline and follow-up (after 13 months, range 15-63 months) HRCT scans of 14 consecutive patients with sarcoidosis were reviewed by a single observer. Each follow-up HRCT examination was assessed as stable, improved (when the extent of HRCT findings was reduced compared with baseline) and worsened (when the extent of HRCT findings was increased and/or when HRCT pattern had become fibrotic compared with baseline). Any increase or decrease in forced vital capacity (FVC)≥10% from baseline was considered significant. Changes on HRCT were then compared with those on FVC. RESULTS: During a median follow-up of 33 (range 15-63) months, HRCT findings worsened in 8/14 (58%) cases, improved in 3/14 (21%) and remained stable in 3/14 (21%). Agreement between changes on HRCT and FVC was moderate (κ=0.49). In 9/14 (64%) cases, HRCT changes were in line with those on FVC. In 4/5 discordant cases, the worsened HRCT findings were not mirrored by FVC changes. CONCLUSIONS: Despite the small size of our study population, our results suggest that HRCT may provide clinicians with additional information about the evolution of sarcoidosis.

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 individual's disability and the presence of osteoporosis were independently associated with poorer rehabilitation outcomes.

Bronchial vascular remodelling in patients with COPD and its relationship with inhaled steroid treatment.

BACKGROUND: Only a few studies have evaluated microvascular changes and proangiogenetic mediators in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and the results have been discordant. Furthermore, the role of inhaled corticosteroids (ICS) in COPD has not been extensively studied. A study was undertaken to evaluate vascular remodelling, its relationship with inflammatory cells and treatment effects in the bronchial mucosa of patients with COPD. METHODS: The study comprised three groups: (1) 10 non-treated patients with COPD (COPD); (2) 10 patients with COPD treated with nebulised beclomethasone dipropionate 1600-2400 mug daily (equivalent to 800-1200 mug via metered dose inhaler) (COPD/ICS); and (3) 8 control subjects (CS). Bronchial biopsies were evaluated for number and size of vessels and vascular area. Specimens were also examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) expression and inflammatory cell counts were performed. RESULTS: Vascular area, vessel size, VEGF+ cells, bFGF+ cells and TGF-beta+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (all p<0.05). In addition, bFGF+ cells were significantly increased in the COPD/ICS group compared with the CS group, and CD8+ and CD68+ cells were significantly increased in the COPD group compared with the COPD/ICS and CS groups (p<0.05). In the COPD group the VEGF+ cells correlated with the number of vessels (p<0.05), vascular area (p<0.01) and vessel size (p<0.05), and TGF-beta+ cells correlated significantly with vascular area (p<0.05). CONCLUSION: Bronchial vascular remodelling in patients with COPD is mainly related to morphological changes of the mucosal microvessels rather than to new vessel formation, and may be reduced in patients treated with steroids.

Carfilzomib: A Tale of a Heartbreaking Moment: Case Report and Concise Review of the Literature.

BACKGROUND: Carfilzomib, a proteasome inhibitor, known as a therapeutical option for people who have already received one or more previous treatments for multiple myeloma, has well known cardiac and systemic adverse effects. OBJECTIVE: There is evidence supporting that adverse effects are dose dependent, yet there is no known patient phenotype characterized by worse associated consequences, nor are there widely accepted monitoring protocols. RESULTS: In this article we describe two patients with cardiovascular adverse events related to carfilzomib treatment and their clinical course. Our goal was to present two cases of daily practice, which highlighted the complexity of their management and led to underline how baseline evaluation and close follow-up with echocardiography and cardiac biomarkers, including natriuretic peptides, remain an important tool for the cardiotoxicity surveillance. CONCLUSION: These reflections should lead to further studies in order to identify high risk patients for cardiovascular adverse event and clarify the real incidence of cardiotoxicity of this drug and adequate follow-up timing. Finally further research is needed to evaluate strategies for prevention and attenuation of cardiovascular complications of cancer therapy.

Assessment and monitoring of ventilatory function and cough efficacy in patients with amyotrophic lateral sclerosis.

Assessing and monitoring respiratory muscle function is crucial in patients with Amyotrophic Lateral Sclerosis, since impaired function can lead to either ventilatory failure or respiratory tract infection. Spirometry, diffusing capacity of the lung, breathing pattern, sleep study, blood gas analysis and respiratory muscle strength tests, as well as cough peak flow and cough expiratory volume measurements can provide relevant information on ventilatory function and cough efficacy. With regard to respiratory muscle strength testing, the rational approach consists in starting with volitional and non-invasive tests and later using invasive and non-volitional tests. This review focuses on both ventilatory and respiratory muscle strength testing, in order to undertake a timely treatment of respiratory failure and/or impaired cough efficacy. So far, the current literature has not highlighted any gold standard which stipulates when to commence ventilation and cough support in patients with Amyotrophic Lateral Sclerosis. A composite set of clinical and functional parameters is required for treatment scheduling to monitor lung involvement and follow-up in these patients.

Lung function and bronchial responsiveness after bronchoalveolar lavage and bronchial biopsy performed without premedication in stable asthmatic subjects.

We evaluated tolerance, safety, and effects on lung function and bronchial responsiveness of BAL (4 x 50 ml) combined with BB (three to five specimens) performed without premedication in 13 mild and stable asthmatics and eight healthy volunteers. All subjects tolerated bronchoscopy procedures well and without serious side effects. During procedures, no supplemental oxygen was administered and no ECG abnormalities were noted. The PEFR was measured before and immediately after bronchoscopy and at 5-min intervals up until recovery. The maximal percentage fall in PEFR after bronchoscopy was significantly greater in asthmatics (23.1 +/- 13.9 percent) compared to normal subjects (7.8 +/- 8.2 percent, p less than 0.01). Changes in PEFR returned to baseline values within 120 min in all asthmatics. The tcPO2 was recorded at baseline, during and after bronchoscopy. In both groups, a significant change in tcPO2 was measured during the infusion of BAL aliquots, and persisted throughout the procedure. A significant difference in asthmatics compared to healthy subjects was evident during BB and at the end of the procedure (p less than 0.05). In asthmatics, M challenge was performed on three different days over a three-week period prior to bronchoscopy, and was repeated at intervals of 2, 6, and 24 h following procedure. The PC20 M values measured before bronchoscopy were found to have a very high reproducibility (intraclass correlation coefficient = 0.93). The PC20 values measured during experiment times after bronchoscopy were not significantly different from baseline values. These data demonstrate that in mild and stable asthmatics, BAL combined with BB can be safely performed following administration of only local anesthesia. In carefully selected asthmatic subjects, transient bronchoconstriction and a lowering of oxygen tension can be induced by BAL and BB, whereas changes in bronchial responsiveness are more unlikely to occur.

Provocative dose and dose-response curve to inhaled propranolol in asthmatic patients with bronchial hyperresponsiveness to methacholine.

This study was carried out to compare bronchial responses to inhaled propranolol (P) and methacholine (M) in a group of asthmatic subjects with mild to moderate bronchial hyperresponsiveness to M; to determine the short term reproducibility of bronchial response to propranolol; and to examine the shape of dose-response curve to P relative to that of M. Doses of M and P were given in mumoles and bronchial responses to both agents were expressed as the provocative dose that induced a 20 percent fall in FEV1 (PD20 FEV1). In 16 asthmatic patients, there was no correlation between the PD20 of the two agents. Mean PD20 M (+/- SD in log scale) was approximately nine times lower than mean PD20 P (0.64 +/- 0.96 and 5.80 +/- 1.65, respectively). This difference was statistically significant (t = 4.58, p less than 0.001). In six asthmatic patients, the reproducibility of PD20 P was similar to that of M (intraclass correlation coefficient 0.969 and 0.957, respectively). The shape of the dose-response curves to P was different from that of M in five of nine asthmatic patients when all experimental points were analyzed by double-reciprocal plot. We noticed that even small doses of inhaled P may cause a severe bronchoconstriction. Therefore, special caution should be taken to increase P doses very gradually, when studying the dose-response curve. We demonstrated that P inhalation induced a measurable bronchoconstriction in subjects with mild to moderate hyperresponsiveness and it was reproducible. However, the bronchial sensitivity to P was lower than to M. Our findings suggest that P and M have different mechanisms of action.

Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission.

Bronchoalveolar lavage and BB were performed in 13 asthmatic and six healthy subjects to characterize cellular markers of inflammation in BAL and BB; to compare cellular profile of BAL with cell infiltration in BB; to examine the relationship between bronchial responsiveness and markers of inflammation in BAL and BB. Eosinophils and mast cells were increased in BAL in asthmatic subjects; eosinophils were positively correlated with neutrophils and mast cells. Epithelial shedding was present in nine asthmatic and five control subjects. Intraepithelial cells and cells in submucosa were increased in asthmatic subjects. Eosinophils and intraepithelial mast cells were higher. Thickened basement membrane was associated with more marked cell infiltration in submucosa. Ciliated cells in BAL relate to intraepithelial cells; cells in BAL broadly reflect cell infiltration of submucosa. In the asthmatic group, the degree of bronchial responsiveness correlated with ciliated cells in BAL and with intra-epithelial cells in BB. Marked airway inflammation is associated with stable asthma; inflammatory changes within bronchial epithelium may be linked to the development of bronchial hyperresponsiveness.

Airways remodeling is a distinctive feature of asthma and is related to severity of disease.

PURPOSE: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS: Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS: We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.

The effect of inflammation on mucociliary clearance in asthma: an overview.

Mucociliary clearance (MCC) is one of the most important nonspecific defense mechanisms of the respiratory tract, and its impairment is a well-documented feature of chronic respiratory diseases, including asthma. In vitro and in vivo data suggest that several inflammatory mediators influence the mucociliary apparatus. Epithelial damage and functional abnormalities have been described in bronchial asthma, along with changes in mucus-secreting cells and the chemical and rheological properties of airway fluid. Although the mechanisms of MCC impairment in asthma are not clearly understood, data in the recent literature suggest that airway inflammation plays a major role. In this article, we review studies on MCC alterations in light of up-to-date findings on pathogenetic mechanisms in asthma.

Induced sputum in patients with newly diagnosed sarcoidosis: comparison with bronchial wash and BAL.

OBJECTIVES: Sarcoidosis is characterized by a diffuse alveolar inflammatory process, although bronchial airways are often involved. This study compares the cellular profiles of induced sputum (IS), bronchial washing (BW), and BAL in newly diagnosed sarcoidosis patients to those in control subjects, and examines whether inflammatory cell counts from IS are correlated with inflammatory cell counts from BW and BAL in sarcoidosis patients. PATIENTS AND MEASUREMENTS: We recruited 15 untreated patients with stage I and II pulmonary sarcoidosis and 12 healthy volunteers. Sputum was induced with hypertonic saline solution in all individuals. Bronchoscopy was performed on a different occasion in all patients and in five control subjects. RESULTS: Mean lymphocyte counts in IS, BW, and BAL fluid from sarcoidosis patients were significantly higher than in control subjects (9.4% vs 3.8%, p < 0.05; 12.6% vs 3.9%, p < 0.05; 24.1% vs 2.6%, p < 0.05, respectively). Moreover, total cell count and percentage of epithelial cells in IS were significantly higher in sarcoidosis patients than in control subjects (p < 0.01 and p < 0.05, respectively). In sarcoidosis patients, comparison between different samples showed significantly higher percentages of macrophages in BW and BAL than in IS (p < 0.05 and p < 0.01, respectively), whereas the percentage of neutrophils was higher in IS compared with BW and BAL (p < 0.01 and p < 0.001, respectively). Finally, the percentage of lymphocytes in IS was significantly lower than that in BAL (p < 0.05) but not that in BW. CONCLUSIONS: We demonstrated that, compared with IS in healthy control subjects, IS in untreated pulmonary sarcoidosis patients contains more total cells, lymphocytes, and epithelial cells. Although the relative proportion of inflammatory cells in the three samples differed, lymphocyte counts in IS were high. This finding suggests that IS could be used as a valuable alternative to more conventional invasive techniques in clinical assessment of pulmonary sarcoidosis patients.

Effect of sputum induction on spirometric measurements and arterial oxygen saturation in asthmatic patients, smokers, and healthy subjects.

BACKGROUND: Sputum production induced by inhalation of hypertonic saline solution has been proposed as a technique to collect secretions and inflammatory cells from the airways of subjects with bronchial asthma or with a history of smoking. The aim of this study was to determine the effect of a sputum induction procedure on spirometric results and arterial oxygen saturation (SaO(2)) in asthmatic patients, smokers, and healthy subjects. METHODS: We recruited 14 subjects suffering from asthma (11 men and 3 women; age range, 18 to 49 years), 14 subjects with a history of smoking (5 men and 9 women; age range, 23 to 64 years), and 9 healthy volunteers (7 men and 2 women; age range, 28 to 54 years). To obtain a sample of induced sputum, all subjects inhaled a mist of 3% hypertonic saline solution nebulized for 5 min and repeated the cycle no more than four times. Asthmatic patients were pretreated with 200 microg salbutamol (inhaled). During sputum induction, the transcutaneous SaO(2) was continuously measured and baseline, fall, and the differences between baseline and fall SaO(2) were recorded. Additionally, we measured the duration of mild desaturation (change in SaO(2), < 4%) and of marked desaturation (change in SaO(2), > 5%) in each subject. Finally, baseline FEV(1) and changes in FEV(1) as a percentage of baseline values were recorded in all subjects. RESULTS: We found that baseline and fall SaO(2) values for the three groups were similar. However, in each group a significant mean change in SaO(2) was evident during sputum production (asthmatic patients, 6.0%; smokers, 5.3%; healthy subjects, 6.0%). Moreover, the mean durations of mild desaturation were 7 min, 21 s in asthma patients; 8 min, 24 s in smokers; and 7 min, 16 s in healthy subjects. Similarly, the durations of marked desaturation were 1 min, 25 s in asthmatic patients, 1 min, 19 s in smokers, and 1 min, 21 s in healthy subjects. The mean (+/- SD) fall in FEV(1) was not statistically different among the three groups (asthmatic patients, 1.36 +/- 5.6%; smokers, 7.58 +/- 11.76%; and healthy subjects, 0.05 +/- 9.6%). However, one smoker did experience excessive bronchoconstriction (fall in FEV(1), > 20%). CONCLUSIONS: This study demonstrated a significant and comparable fall in SaO(2) during sputum induction by inhalation of hypertonic saline solution in asthmatic patients, smokers, and healthy subjects. The results suggest that subjects who are hypoxemic before sputum induction require SaO(2) monitoring during the procedure.

Lung epithelial permeability and bronchial responsiveness in subjects with stable asthma.

Lung epithelial permeability of asthmatic patients has been reported to be similar or lower than that of healthy subjects and to be correlated or not to bronchial hyperresponsiveness. To clarify these discrepancies, we evaluated 99mTc-DTPA pulmonary clearance in a group of carefully selected asthmatic patients with mild, stable asthma (n = 13; seven women; mean age +/- SD = 27.69 +/- 6.63 years), and compared them with a group of healthy, nonsmoking subjects (n = 8; six women; mean age +/- SD = 24.38 +/- 5.15 years). Selection criteria for asthmatics were as follows: baseline FEV1 > or = 80% of predicted values, no bronchial infections, and/or no asthma attacks during 4 weeks prior to study and peak expiratory flow rate variability lower than 20%, over a period of 3 weeks. Patients controlled symptoms with beta 2-adrenergic drugs only, regularly or on demand. Mean baseline FEV1 (+/-SD) as percent of predicted was 102.38 +/- 13.97 and 112.88 +/- 18.36, respectively (p < 0.05). In the asthmatic group, bronchial responsiveness to methacholine (PC20 M FEV1) ranged between 0.55 and 28.5 mg/mL. Mean value (+/-SD) of DTPA clearance from lungs to blood (evaluated on the first 10 min out of 30 min of the curves) in the asthmatic group was not different from that of control group (68.31 +/- 21.46 and 69.5 +/- 15.73). In the asthmatic patients, there was no correlation between PC20 M values and DTPA T1/2 min of the whole lung, nor between PC20 M and inner and outer lung clearance zones. Moreover, both in asthmatics and healthy subjects, DTPA clearance of outer (alveolar) zones was significantly faster than that of inner (bronchial) zones (57.69 +/- 19.94 vs 102.08 +/- 38.19, p < 0.001, and 59.75 +/- 12.49 vs 103.5 +/- 31.86, p < 0.003, respectively). Our data show that DTPA clearance in patients with stable asthma is similar to that found in healthy subjects; it is not correlated to degree of bronchial responsiveness and occurs more rapidly in the outer zones than in the inner zones, both in asthmatic patients and in healthy subjects. Thus, to date, DTPA clearance index is not a valid tool for identifying and/or monitoring asthmatic patients.

Relationship between outcome measures of six-minute walk test and baseline lung function in patients with interstitial lung disease.

BACKGROUND AND AIM OF THE WORK: In patients with interstitial lung disease (ILD), the six-minute walk test (6MWT) has been rarely used, and up till now, the relationship between outcome measures of the test and baseline lung function has not yet been examined. Therefore, we assessed walk distance, oxygen desaturation, and breathlessness perception during 6MWT, and their relationships to baseline lung function in patients with ILD. METHODS: Forty ILD patients with history of breathlessness during physical exertion performed a 6MWT following a standard protocol. Breathlessness perception during walk was assessed by visual analogue scale (VAS, in mm). RESULTS: The mean walk distance was 487 meters (range 271-689). Mean baseline oxygen saturation (Base SpO2, %) was 94% and was reduced during walk, either as mean oxygen saturation (Mean SpO2, 89%, p < 0.001) or as mean fall in oxygen saturation during walk (Fall SpO2, 5%). Furthermore, VAS significantly increased after walk (5 mm to 44 mm, p < 0.001). A close relationship of TLco and TLC to walk distance and Fall SpO2 was found (r = 0.45 and 0.42 and r = -0.75 and -0.64, respectively; p < 0.001, each). On the basis of regression equations by stepwise multiple regression analysis, walk distance was predicted by age and FVC (r2 = 0.50), Mean SpO2 by TLco and Base SpO2 (r2 = 0.80), and Fall SpO2 only by TLco (r2 = 0.57). Breathlessness perception was not reliably predicted by any assessed variables. CONCLUSIONS: We confirmed that 6MWT provides a global evaluation of sub-maximal exercise capacity in ILD patients. We also found that walk distance and oxygen desaturation, but not breathlessness perception during walk, are strictly related to baseline lung function.

Eosinophils in induced sputum from asymptomatic smokers with normal lung function.

Cigarette smoking is the dominant risk factor for chronic obstructive pulmonary disease (COPD). However, only 10-15% of smokers develop the disease and early changes within the airways are poorly defined. We aimed to compare cell profiles in induced sputum (IS) from asymptomatic smokers to that from healthy subjects, and to ascertain whether or not inflammatory cells in IS are related to lung function and smoking habit. We recruited 34 heavy, non-allergic asymptomatic smokers with normal lung function and 15 healthy volunteers, who performed lung function tests and IS by hypertonic saline (3%) solution. In smokers, significantcorrelation between pack-years and FEF25-75 (rs = -0.43, P < 0.02) was found. In IS, smokers had higher counts of macrophages (P < 0.01) and eosinophils (P < 0.02), when compared to those of healthy subjects. Additionally, eosinophils were found in IS of 14 out of 34 smokers, with eosinophils had a higher pack-years (31 +/- 25 vs. 13 +/- 10, P = 0.02) and lower FEF 25-75% value (78% +/- 34 vs. 100% +/- 23. P < 0.04). when compared to smokers without eosinophils. Additionally, on the basis of regression equations by stepwise multiple regression analysis, eosinophils were predicted by pack-years (r2 = 0.41). Our results showed that asymptomatic smokers have evidence of inflammatory cells in IS samples. In addition, we found thatthe degree of eosinophilic inflammation is related to early changes of lung function and can be predicted by smoking habit.

Six-minute walking test in cystic fibrosis adults with mild to moderate lung disease: comparison to healthy subjects.

The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities.

[Educational programs and self-management in bronchial asthma]. / Programmi educazionali e self-management nell'asma bronchiale.

Bronchial asthma is one of the most common chronic diseases in the world and can affect people of all ages. In the last few years there has been a considerable improvement in the etiopathogenetic knowledge of the disease and extremely effective anti-asthmatic drugs are available. However, asthma-related morbidity and mortality are increased, especially in Western countries. In an attempt to reverse this negative trend, for a number of years national and international guidelines on asthma have been published all over the world. These guidelines have the aim of improving asthma diagnosis and treatment and of conveying a fundamental educational message both to health workers and to patients and their families. From the data in the literature it can be clearly seen that only through the application of valid educational programs is it possible for asthmatics to improve their knowledge of the disease and to understand how they can look after themselves by a careful evaluation of their own symptoms and respiratory function. They should also be aware of the drugs available for the treatment of both acute asthmatic crises and chronic asthma, but especially of the fact that this chronic inflammatory affection can be fully treated. In particular, an educational program organized with groups of maximum 10-12 people attending 2 lessons and with helpful training tools, can increase significantly asthma knowledge, treatment compliance and patient self-management. The aim of this review is to highlight the importance of educational programs and those obscure areas which slow down their large scale application and universal acceptance.