Search

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P 0.02; healthy subjects: P 0.03), whereas EBC PGE2 was elevated in current (P = 0.0065) and ex-smokers with COPD (P = 0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P 0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P 0.01; healthy subjects: P 0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P = 0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimer's disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p ≤ 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.

Water-soluble extracts of cigarette smoke are easily formed in some body compartments, such as saliva or fluid lining alveolar spaces, and can act on both cellular and extracellular compartments. In this paper we have analysed the effect of aqueous smoke extract on some metabolic and functional aspects of polymorphonuclear leukocytes. In particular, the following cellular aspects were studied: chemiluminescence, glycolysis, membrane fluidity and microscopic interaction with zymosan particles. While chemiluminescence and glycolytic activity are highly inhibited, no effect of smoke extract on membrane fluidity was observed. Moreover, the response of luminol-dependent chemiluminescence was significantly delayed, while that of lucigenin-dependent chemiluminescence was anticipated. Furthermore, the phagocytic ability of neutrophils pretreated with aqueous smoke extract was also significantly hindered. All these results might indicate that the finely tuned activity of polymorphonuclear leukocytes is somehow hampered by the aqueous extract of cigarette smoke in a way which makes these cells less effective against bacteria and more noxious towards surrounding tissues.

The nonallergic rhinitis with eosinophilia syndrome (NARES) is a type of chronic rhinitis, characterized by intense (> 20%) eosinophilia of the nasal secretions. In this study, screening for NARES in 81 patients with nonallergic chronic rhinitis was performed using a modified nasal lavage cytometric method. Twenty-one of the 81 investigated individuals (25.9%) showed nasal eosinophilia greater than 20%, therefore being diagnosed as having NARES. No statistical difference in total serum IgE concentration (Prist Pharmacia) was observed between the NARES subjects and those with other forms of chronic rhinitis, confirming the seemingly nonallergic nature of NARES. In 28.6% of these cases the presence of anosmia was detected: in 19.0% of cases with NARES (all subjects complaining of long-lasting symptoms and suffering from anosmia), nasal polyposis coexisted. Our results confirm that nasal lavage cytometry may represent a useful clinical tool in the diagnosis of chronic rhinitis.

a b s t r a c t Introduction: Endobronchial ultrasound (EBUS) can be used as an alternative to fluoroscopy to visualize a peripheral pulmonary lesion (PPL) and to provide an image guidance for transbronchial biopsy (TBB). The aim of this study was to verify the accuracy of EBUS-guided TBB in the diagnosis of PPLs. Methods: All the patients with CT-scan evidence of PPL who underwent bronchoscopy with EBUS in the period between 2008 and 2011 were retrospectively evaluated. EBUS was performed using a radial-type miniature ultrasound probe. Once obtained an EBUS image of the PPL, we measured the distance of the PPL from the outer orifice of the working channel of the bronchoscope in order to perform TBB at PPL site. Results: A total of 662 patients were examined. The mean diameter of lesions was 36 ± 20 mm. PPLs were visualized in 494 patients (75%) and the TBB was performed in 479 patients. Thirty-two patients were lost in follow-up and data from 447 patients were analyzed. TBB results were 255 cancers and 192 non-malignant lesions. The final diagnosis reported was 359 cases of cancer and 88 of benign lesion. EBUS-guided TBB had a sensitivity of 71% for the diagnosis of cancer, a negative predictive value of 46% and an overall diagnostic accuracy of 77%. Conclusions: These data obtained from a large series of patients and using an original method show that EBUS represents a valid support to bronchoscopy and that the EBUS-guided TBB has a high diagnostic yield in the diagnosis of PPLs.

"Electronic noses (e-noses), artificial sensor systems generally consisting of chemical sensor arrays for the detection of volatile compound profiles, have potential applications in respiratory medicine. We assessed within-day and between-day repeatability of an e-nose made from 32 sensors in patients with stable chronic obstructive pulmonary disease (COPD). We also compared between-day repeatability of an e-nose, fraction of exhaled nitric oxide (F ENO) and pulmonary function testing. Within-day and between-day repeatability for the e-nose was assessed in two breath samples collected 30 min and seven days apart, respectively. Repeatability was expressed as an intraclass correlation coefficient (ICC). All sensors had ICC above 0.5, a value that is considered acceptable for repeatability. Regarding within-day repeatability, ICC ranged from 0.75 to 0.84 (mean = 0.80 ± 0.004). Sensors 6 and 19 were the most reproducible sensors (both, ICC = 0.84). Regarding between-day repeatability, ICC ranged from 0.57 to 0.76 (mean = 0.68 ± 0.01). Sensor 19 was the most reproducible sensor (ICC = 0.76). Within-day e-nose repeatability was greater than between-day repeatability (P < 0.0001). Between-day repeatability of FENO (ICC = 0.91) and spirometry (ICC range = 0.94-0.98) was greater than that of e-nose (mean ICC = 0.68). In patients with stable COPD, the e-nose used in this study has acceptable within-day and between-day repeatability which varies between different sensors. "

Background β-thymosins play roles in cytoskeleton rearrangement, angiogenesis, fibrosis and reparative process, thus suggesting a possible involvement in the pathogenesis of systemic sclerosis. The aim of the study was to investigate the presence of thymosins β4, β4 sulfoxide, and β10 in bronchoalveolar lavage fluid of scleroderma patients with interstitial lung disease and the relation of these factors with pulmonary functional and radiological parameters. Methods β-thymosins concentrations were determined by Reverse Phase-High Performance Liquid Chromatography-Electrospray-Mass Spectrometry in the bronchoalveolar lavage fluid of 46 scleroderma patients with lung involvement and of 15 controls. Results Thymosin β4, β4 sulfoxide, and β10 were detectable in bronchoalveolar lavage fluid of patients and controls. Thymosin β4 levels were significantly higher in scleroderma patients than in controls. In addition, analyzing the progression of scleroderma lung disease at one-year follow-up, we have found that higher thymosin β4 levels seem to have a protective role against lung tissue damage. Thymosin β4 sulfoxide levels were higher in the smokers and in the scleroderma patients with alveolitis. Conclusions We describe for the first time β-thymosins in bronchoalveolar lavage fluid and their possible involvement in the pathogenesis of scleroderma lung disease. Thymosin β4 seems to have a protective role against lung tissue damage, while its oxidation product mirrors an alveolar inflammatory status.

Some studies have raised the question of the need for chronic controller therapy in mild persistent asthma as suggested by international guidelines. Although the Improving Asthma Control (IMPACT) and Beclomethasone plus Salbutamol (BEST) studies suggest that on-demand therapy in some patients with mild persistent asthma achieves a similar degree of asthma control based on symptoms and functional outcomes, the IMPACT study indicates that regular and on-demand therapy is not equivalent for controlling airway inflammation. Persistent airway inflammation might lead to airway remodelling with onset or worsening of symptoms, deterioration in lung function, and reduced response to pharmacological therapy. However, the relationships between chronic airway inflammation and airway remodelling need to be clarified. Choosing the ‘right’ pharmacological strategy (regular versus on-demand treatment) for asthma control is currently difficult due to the fact that (1) inflammatory outcome measures were not generally incorporated into asthma clinical trials; (2) the relationships between chronic airway inflammation and airway remodelling are largely unknown; (3) current clinical asthma trials that are generally based on symptomatic and functional outcome measures are too short to assess the impact of regular anti-inflammatory therapy on natural history of asthma; (4) asthma is an heterogeneous disease and different phenotypes of asthma patients likely requiring a different therapeutic approach can be identified, even in the same class of asthma severity. Guidelines for asthma management are valuable tools, although they are necessarily based on a strategy directed to the best outcome in a group of patients. Asthma phenotyping is becoming central for asthma management. The issue of regular versus on-demand treatment of intermittent and mild persistent asthma would be better addressed if considered within an individualized approach to asthma management and assessment. Identification of clinical, functional, morphological and biochemical phenotypes of patients with asthma and its clinical implications is likely to lead to a tailored, individualized, pharmacological therapy and asthma management.

Background. This study aimed to assess the diagnostic yield of autofluorescence bronchoscopy (AFB) in the detection of pre-cancerous bronchial lesions in a non-selected sample of patients. Methods. Both fiberoptic white-light bronchoscopy (WLB) and AFB using the Storz D-light system were performed on 166 consecutive patients. Biopsy specimens were taken in areas of the tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. The bronchoscopic procedures were randomly performed by two operators. Results. A total of 93 patients had a positive biopsy specimen: 80 for cancer and 13 for dysplasia. AFB was abnormal or suspicious in 85 of the 93 patients with a sensitivity of 91.4%. Specificity was 50.7%. In 16 patients with normal WLB examination, AFB identified abnormal or suspicious areas which had a positive biopsy. Thus AFB significantly improved sensitivity of WLB (100% vs 82.8%, respectively, p

An iCycler iQ real-time PCR assay targeting 18S rRNA Aspergillus -specific sequences was developed for the diagnosis of invasive pulmonary aspergillosis (IPA). Positive findings were obtained for 18 of 20 (90%) bronchoalveolar lavage (BAL) fluid specimens from patients with probable or confirmed IPA and were obtained for none of the 24 BAL samples from patients with no clinical evidence of aspergillosis. These results were concordant with those of a nested PCR assay, which detected 90% of the patients with IPA, while galactomannan ELISA revealed positivity for 100% of these patients, suggesting that combined use of methods might improve the diagnosis of IPA.

BackgroundA progressive lung disease and a worse survival have been observed in patients with systemic sclerosis and alveolitis. The objective of this study was to define the functional, radiological and biological markers of alveolitis in SSc patients.Methods100 SSc patients (76 with limited and 24 with diffuse disease) underwent a multistep assessment of cardiopulmonary system: pulmonary function tests (PFTs) every 6–12 months, echocardiography, high resolution computed tomography (HRCT) and bronchoalveolar lavage (BAL), if clinically advisable. Alveolar and interstitial scores on HRCT and IL-6 plasma levels were also assessed as lung disease activity indices.Results90 SSc patients with abnormal PFTs and 3 with signs and/or symptoms of lung involvement and normal PFTs underwent HRCT and echocardiography. HRCT revealed evidence of fibrosis in 87 (93.5%) patients, with 55 (59.1%) showing both ground glass attenuation and fibrosis. In 42 patients who had exhibited ground glass on HRCT and consented to undergo BAL, 16 (38.1%) revealed alveolitis. 12 (75%) of these patients had restrictive lung disease (p < 0.0001) and presented diffuse skin involvement (p = 0.0009). IL-6 plasma levels were higher in patients with alveolitis than in patients without (p = 0.041). On logistic regression model the best independent predictors of alveolitis were diffuse skin involvement (OR(95%CIs):12.80(2.54–64.37)) and skin score > 14 (OR(95%CIs):7.03(1.40–34.33)). The alveolar score showed a significant correlation with IL-6 plasma levels (r = 0.36, p = 0.001) and with the skin score (r = 0.33, p = 0.001). Cultures of BAL fluid resulted positive in 10 (23.8%) of the 42 patients that underwent BAL and after one year a deterioration in PFTs occurred in 8 (80%) of these patients (p = 0.01). Pulmonary artery systolic pressure ≥ 40 mmHg was found in 6 (37.5%) patients with alveolitis.ConclusionWe found alveolitis only in 38.1% of the patients who had exhibited ground glass on HRCT and then underwent BAL, probably because the concomitant fibrosis influenced results. A diffuse skin involvement and a restrictive pattern on PFTs together with ground glass on HRCT were judged possible markers of alveolitis, a BAL examination being indicated as the next step. Nevertheless BAL would be necessary to detect any infections of the lower respiratory tract that may cause further deterioration in lung function.

Some analogy exists between cognitive impairment in hypoxemic patients with chronic obstructive pulmonary disease (COPD) and Alzheimer's disease (AD). We purposed to verify whether the analogy extends to the cerebral perfusion pattern. Ten normal subjects, 15 COPD patients with and 18 without hypoxemia, and 15 patients with mild AD matched for age and educational level underwent brain perfusion single photon emission computed tomography (SPECT) and neuropsychological assessment. Normal subjects and non hypoxemic COPD patients had comparable perfusion patterns. The average perfusion decreased from non hypoxemic to hypoxemic COPD and, then, to AD patients. Hypoperfusion of associative areas was the hallmark of AD, whereas the average perfusion of anterior cortical and subcortical regions did not distinguish AD and hypoxemic COPD patients. Both COPD groups scored higher than AD patients (p/= 0.01) in 13 cognitive tests but below the normal in selected tests of verbal attainment, attention and deductive thinking. Perfusion of anterior cortical and subcortical regions of the dominant hemisphere was directly correlated with the number of correctly performed neuropsychologic tests. In conclusion, anterior cerebral hypoperfusion and selected neuropsychological dysfunctions characterized hypoxemic COPD patients and could herald frontal-type cognitive decline with the worsening of the hypoxemia.

Purpose To identify factors affecting the shortterm prognosis of patients with acutely exacerbated chronic obstructive pulmonary disease (COPD). Patients and Methods The 590 patients having COPD as primary disease who were hospitalized in the pneumology unit of a university hospital from 1981 to 1990 were studied. A standardized protocol for the treatment of acutely exacerbated COPD was adopted for all the patients. The patient records were retrospectively analyzed by two observers, and 23 clinical and laboratory variables defining the patient status on admission were collected. Age and arterial gas data were also taken into account, and the outcome mortality was recorded. Interobserver reproducibility was tested by computing the κ coefficient and Spearman's p for dichotomous and continuous variables, respectively. The relationship of clinical and laboratory factors to the outcome was assessed first by univariate analysis and then by a logistic regression analysis assessing the independent predictive role of variables previously shown to be univariately correlated with mortality. Results The mortality rate was 14.4%. The logistic regression analysis identified four independent predictors of death: age (odds ratio [OR]1.07; 95% confidence interval [CI]1.04 to 1.11), alveolar-arterial oxygen gradient greater than 41 mm Hg (OR 2.33; 95% CI 1.39 to 3.90), ventricular arrhythmias (OR 1.91; 95% CI 1.10 to 3.31), and atrial fibrillation (OR 2.27; 95% CI 1.14 to 4.51). Conclusions Patients with acutely exacerbated COPD having a high risk of death can be identified at the time of admission. Variables reflecting heart dysfunction are important determinants of this risk. Among pulmonary function data, only alveolar-arterial oxygen gradient contributes to the predictive model.

Bilateral bronchoalveolar lavage (BAL) was carried out in right middle and left upper lobes of 22 nonsmoking females suffering from progressive systemic sclerosis in order to assess interlobar differences and functional correlation of the BAL composition. The patients' age ranged from 20 to 66 years, and the mean disease duration was 10.4 years. The most frequent finding was a mild BAL lymphocytosis (right in 11 of 22 patients; left in 8 of 22), but eosinophilic (right in 11 of 22; left in 5 of 22 patients) and neutrophilic (right in 9 of 22 patients; left in 1 of 22) alveolitis was recognized as well. Differential counts suggestive of alveolitis limited to one of the lavaged lobes were demonstrated in about one fourth of the cases. Including increased cellularity among the criteria of pathological BAL fluid composition, 14% of the subjects showed bilateral BAL results within the normal range. OKT8-positive lymphocytes were significantly increased in 3 patients, but the mean values were not. Total lung capacity, vital capacity, and forced expiratory volume in 1 s correlated inversely with BAL neutrophil (p less than 0.05) and granulocytic (p less than 0.01) differential counts; the strongest, positive correlation was demonstrated regarding the lymphocyte/granulocyte ratios (p less than 0.0005). In conclusion, several patterns of alveolitis as well as a bilaterally normal BAL composition were found in our series; moreover, even if inhomogeneous alveolitis did occur, a single lavage performed in the right middle lobe correctly detected or excluded the presence of an alveolitis in 95% of our patients.

Background —Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. Methods and Results —Two hundred sixty-three patients (217 men) with COPD, mean age 67±9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or ≥1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3.45 years, respectively; Mantel-Cox test, 9.58; P =0.002). The Cox regression analysis identified S 1 S 2 S 3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (P ao 2 −Pa o 2 ) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S 1 S 2 S 3 pattern and RAO (n=14) and of patients having either S 1 S 2 S 3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively ( P =0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their P ao 2 −Pa o 2 during oxygen therapy was or was not >48 mm Hg. Conclusions —Some ECG signs of CCP and P ao 2 −Pa o 2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis.

Data reported by Dr. Sing et al. ([3][1]) about Pneumocystis carinii carriage in immunocompetent adults with primary pulmonary disorders differ partially from our results. We have analyzed 81 bronchoalveolar lavage fluid samples (BALs) from 78 patients (37 male and 41 female; mean age, 57.8 years

The chemiluminescence of peripheral blood monocytes and alveolar macrophages was determined in the presence of luminol and lucigenin, either before or after the cell adherence to the luminometer curvettes. In the case of monocytes, cell adherence induces an increase of luminol-dependent chemiluminescence and has almost no effect on the lucigenin-dependent chemiluminescence. However, it shows a strong inhibition of the lucigenin-dependent chemiluminescence and almost no effect on luminol-dependent chemiluminescence, in the case of alveolar macrophages. These results show that adhesion to plastic alters the metabolic burst of both monocytes and alveolar macrophages. Although the mechanisms are poorly understood, they seem to be related to the modifications that take place during the differentiation of peripheral monocytes to alveolar macrophages.

In the aetiological diagnosis of pulmonary infections in patients affected by haematological malignancies we evaluated the utility of bronchoalveolar lavage (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our series, we identified the agent of pneumonia in 53.5% of episodes with the best results in aspergillosis, very common in these patients. The previous empirical anti-infective treatment was modified in 14 episodes (11%). The procedure was generally well tolerated and only one patient bled. We maintain that BAL is a useful diagnostic tool for detecting the agents of pulmonary infections in patients with haematological malignancies, especially when the routine microbiological procedures fail, and it also represents a good alternative to more invasive procedures.