High-resolution computed tomography evaluation of airway distensibility in asthmatic and healthy subjects.

PURPOSE: Airway-wall remodelling may result in reduced airway distensibility in bronchial asthma. This study evaluated the baseline airway calibre and distensibility in asthmatic patients by means of high-resolution computed tomography (HRCT). MATERIALS AND METHODS: We studied seven patients (two men, age range 36-69 years) with chronic asthma [forced expiratory volume in the first second (FEV(1)) range: 30%-87% of predicted; FEV1/forced vital capacity (FVC) range 48%-75% of predicted) under stable clinical conditions and six healthy control subjects (three men, age range 29-50 years). In all subjects, HRCT scanning, at suspended end-expiratory volume, was performed at rest and during ventilation with 6 and 12 cmH(2)O by nasal insufflation with continuous positive airway pressure (nCPAP), both at baseline and after inhalation of 200 mug oxitropium bromide metered dose inhaler (MDI). External and lumen diameter (mm) of the right apical upper lobe bronchus were measured in all HRCT scans. RESULTS: In asthmatics, 12 cmH(2)O insufflation significantly changed baseline lumen (3.3+/-0.7 mm vs. 3.8+/-0.6 mm; p<0.01) and external diameter (6.2+/-0.9 mm vs. 6.7+/-0.8 mm; p<0.05), whereas in healthy controls, both 6 and 12 cmH(2)O insufflation significantly changed baseline lumen diameter (4.0+/-1.6 mm vs. 4.8+/-1.6 mm and 4.7+/-1.7 mm; p<0.01). In asthmatic patients, oxitropium bromide inhalation significantly changed baseline lumen diameter (3.3+/-0.7 mm vs. 4.4+/-0.6 mm; p<0.05), whereas the application of 6 or 12 cmH(2)O insufflation did not modify any bronchial diameters. In healthy controls, oxitropium bromide inhalation significantly changed baseline lumen diameter (4.0+/-.6 mm vs. 5+/-1.5 mm; p<0.05). The application of 12 cmH(2)O but not of 6 cmH(2)O induced a significant change in lumen diameter (5.0+/-1.5 mm vs. 6,0+/-1.6 mm; p<0.05). CONCLUSIONS: Our results show that airway distensibility in asthmatic patients, as assessed by HRCT, can differ compared with that of healthy controls. HRCT can provide useful information on airway distensibility.

Microsatellite analysis of induced sputum DNA in patients with lung cancer in heavy smokers and in healthy subjects.

Abnormality in the fragile histidine triade (FHIT), a candidate tumor suppressor gene located in chromosome region 3 (3p14.2), has been frequently found in multiple tumor types, including lung cancer. In this study, the authors assessed the consistency of DNA microsatellite analysis of induced sputum (IS), as compared to that of blood and plasma. They also evaluated the loss of heterozigosity (LOH) and microsatellite instability (MSI) in 3 different loci, D3S1300, D3S1313, and D3S1234, all internal to the FHIT gene, in IS, blood, and plasma from patients with lung cancer, smokers, and healthy subjects. Eighteen patients with lung cancer (3 females, age mean +/- SD: 63 +/- 7 years), 39 smokers (23 females, age mean +/- SD: 57 +/- 6 years and cigarette pack-years mean +/- SD: 34 +/- 12), and 22 healthy nonsmoking subjects (13 females, age mean +/- SD: 63 +/- 5 years) were studied. DNA was extracted from blood, plasma, and IS, by means of a standard method. Analysis of LOH and MSI were performed using a fluorescent polymerase chain reaction (PCR)-based approach, followed by capillary electrophoresis. The ratios between the peak heights (phs), expressed as random fluorescence units, from plasma/blood (p/b) and induced sputum/blood (is/b) in all three loci were considered. The biases (agreement limits) between the mean ph ratio from p/b and is/b of D3S1300, D3S1313, and D3S1234 were respectively 0.07 (- 0.39 to 0.53), 0.016 (- 0.32 to 0.35), - 0.10 (- 0.51 to 0.30) in the patients; - 0.04 (- 0.52 to 0.43), - 0.06 (- 0.31 to 0.18), - 0.08 (- 0.48 to 0.30) in smokers; and - 0.11 (- 0.40 to 0.17), - 0.05 (- 0.53 to 0.43), - 0.09 (- 0.51 to 0.33) in healthy subjects. LOH and MSI in at least one locus were observed in 55% of patients, in 18% of smokers, and in 4.5% of healthy subjects (P < 0.001). These results showed that IS DNA provided data that were consistent with those from blood and plasma. These findings highlight new prospects for early tumor detection by a noninvasive technique based on the analysis of genetic alterations in induced sputum.

Indications for flexible fiberoptic bronchoscopy and its safety in the very elderly.

AIM: To evaluate the indications and the safety of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL), protected specimen brushing (PSB), endobronchial biopsy (EBB), and transbronchial biopsy (TBB) in a population of very elderly patients. METHODS: We performed a retrospective study of all adult patients, aged 50 years or older, who underwent FOB in the Bronchology Unit of the University of Parma Hospital between 1 January, 2003 and 31 April, 2005. Bronchoscopy records of 436 consecutive patients, including 191 patients, 75 yrs of age and older ("very elderly"; = > 75 yrs), were reviewed. RESULTS: Patients aged < 75 years and aged =/> 75 years were no different with regard to gender, BMI, baseline FEV1/FVC ratio, baseline SaO2, and blood pressure. The primary indication in patients aged < 75 years, was to assist in the diagnosis of a pulmonary mass of unknown aetiology (33%) and to remove secretions in the very elderly patients (31%). Indications for FOB and sampling procedures in the two groups were similar. Approximately 30% of patients in each group required supplemental oxygen during the procedure and fever occurred in 9.2% and 10.3% of patients, respectively. Hypertension and bleeding were relatively rare and did not occur more often in the very elderly. CONCLUSIONS: Indication for FOB did not vary with age and adverse events in both groups were uncommon and generally not severe.

Vascular endothelial growth factor up-regulation and bronchial wall remodelling in asthma.

BACKGROUND: There is increasing in vitro evidence to support a role for vascular endothelial growth factor (VEGF), a major regulator of angiogenesis, as a mediator of fibrosis associated with neovascularization. OBJECTIVE: We tested the hypothesis that VEGF is involved both in increased airway mucosal vascularity and in the subepithelial fibrosis of asthmatic patients. METHODS: Bronchial biopsies were performed in 24 asthmatic patients and eight healthy controls. Immunostaining, using computerized image analysis, was performed using monoclonal antibodies against VEGF(+) cells, type IV collagen, to outline the basement membrane thickness, and tryptase and EG2, to identify mast cells and eosinophils, respectively. RESULTS: The counts of VEGF(+) cells (P<0.05), mast cells and EG2(+) cells (both P<0.01) were higher in asthmatics than in controls. The number of vessels, the vascular area in the lamina propria, and the basement membrane thickness were significantly higher in asthmatics than in healthy volunteers (P<0.01). Moreover, in asthmatic patients, the number of VEGF(+) cells was significantly related to the number of vessels (P<0.01), to mast cells (P<0.01) and to basement membrane thickness (P<0.01). A colocalization study also revealed that mast cells were a relevant cellular source of VEGF. High doses of inhaled fluticasone propionate significantly reduced VEGF(+) cells (P<0.05), vessel number (P<0.05), vascular area (P<0.05) and basement membrane thickness (P<0.05) in a subgroup of asthmatic patients. CONCLUSIONS: This study shows that VEGF, in addition to being involved in the vascular component of airway remodelling, may play a role in the thickening of the basement membrane in asthma.

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.

Induced sputum: diagnostic value in interstitial lung disease.

Induced sputum by inhalation of hypertonic saline solution is a noninvasive technique used to collect cellular and soluble material from lung airways. During the past decade, this method has been widely used to assess airway inflammation in asthma and chronic obstructive pulmonary disease, since it produces reliable results and compares favorably to other invasive techniques, such as biopsy and bronchoalveolar lavage (BAL). Induced sputum has been recently used to study interstitial lung disease (ILD), more specifically pneumoconiosis, sarcoidosis, and nongranulomatous ILD. Moreover, results from induced sputum supplied information comparable to BAL findings for occupational lung disease and were able to distinguish sarcoidosis patients from healthy subjects and from patients with nongranulomatous ILD. Although induced sputum had previously provided promising results in assessing patients with ILD, its diagnostic role has not yet been well defined. Further studies of the evaluation by induced sputum of grading of severity, follow-up of disease, and effects of treatment are needed. Additionally, to date no specific studies have been undertaken to evaluate the safety and functional effects of sputum induction on patients with ILD. In conclusion, we think that induced sputum can be used as a complementary tool to BAL both in research and in clinical monitoring of patients with ILD.

Eosinophil apoptosis in induced sputum from patients with seasonal allergic rhinitis and with asymptomatic and symptomatic asthma.

BACKGROUND: Eosinophilic inflammation is known to play an important role in the pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is characterized by morphologic cell changes and leads to recognition and ingestion by macrophages. Apoptosis could be an important mechanism controlling the resolution of tissue eosinophilia. OBJECTIVE: This study was designed to investigate the presence of apoptotic eosinophils in induced sputum of patients with seasonal allergic rhinitis (SAR), when examined during natural pollen exposure and of patients with perennial asthma of different degrees of severity. METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The severity of asthma was assessed by clinical scoring. Sputum was induced following a standard method and differential cell count was estimated. Eosinophils showing cell shrinkage and nuclear coalescence were classified as apoptotic. The number of apoptotic eosinophils was expressed as the percentage of total cells in sputum and as the proportion of apoptotic eosinophils relative to normal bilobed eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in the SA group was significantly greater than that in the SAR and the AA groups (P < .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA group was significantly lower than that in the SAR group (P < .001) and in the SA group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was significantly greater than in the AA group (P < .05) and in the SA group (P < .05). There was no difference in the apoptotic ratio between the AA and SA groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are detectable in induced sputum of allergic patients. Further, the results of our study suggest that apoptosis could be an important mechanism in the control of acute eosinophilic inflammation in patients with SAR exposed to the sensitizing antigens. It appears that the apoptotic mechanism could be less effective in controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic inflammation.

The increased number of very late activation antigen-4-positive cells correlates with eosinophils and severity of disease in the induced sputum of asthmatic patients.

BACKGROUND: Lymphocyte function associate-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late activation antigen-4 (VLA-4) are involved in the infiltration of leukocytes into the tissues. Experimental models of allergic inflammation suggest that VLA-4 could determine the selective recruitment of eosinophils into the inflamed airways. OBJECTIVE: Our purpose was to evaluate the involvement of integrins in eosinophil recruitment in asthma. METHODS: We evaluated by immunocytochemistry the expression of VLA-4, LFA-1, and Mac-1 and their relationship with inflammatory cells and severity of disease in the induced sputum of 20 mild to moderate atopic asthmatic subjects and in 8 healthy subjects. RESULTS: The number of VLA-4+ cells is increased in asthmatic patients and VLA-4 is mainly localized on eosinophils. Furthermore, VLA-4+ cells are significantly related to eosinophils. In contrast, LFA-1 and Mac-1 cellular expressions do not differ between asthmatic and control subjects and are not related to any specific cell type. Eosinophils and VLA-4+ cells are significantly higher in moderately compared with mildly asthmatic patients (P <.01, P <.05) and with healthy control subjects (P <.0005, P <.001). Eosinophils and VLA-4+ cells are also higher in mildly asthmatic patients compared with control subjects (P <.001, P <.005). CONCLUSION: This is the first report demonstrating, by a noninvasive method in humans, that VLA-4+ cells are increased and correlate with the eosinophils in the induced sputum of atopic patients with mild to moderate asthma and that VLA-4 expression is related to the severity of disease.

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.

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.

Eosinophils, mast cells, and basophils in induced sputum from patients with seasonal allergic rhinitis and perennial asthma: relationship to methacholine responsiveness.

OBJECTIVES: We attempted to determine whether inflammation is present in induced sputum of patients with seasonal allergic rhinitis (AR) as compared with those with perennial asthma (AS) and examined its relationship with bronchial responsiveness to methacholine. METHODS: Sputum was induced in 30 patients with seasonal rhinitis in response to grass pollens only and in 15 patients with stable, asymptomatic asthma. The AR group was divided according to methacholine PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24 micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.2 and 19.6 micromol. In the AS group, methacholine PD20 ranged between 0.42 and 2.6 micromol. The percentage of eosinophils and metachromatic cells (alcian blue-positive) was assessed in sputum by light microscopy. Tryptase-positive cells and EG2+ cells were identified by immunocytochemistry with the mouse anti-human mast cell-tryptase monoclonal antibody and the monoclonal anti-eosinophil cationic protein antibody. RESULTS: We found that the number of eosinophils in the AS group was greater than that in the AR+ group (p < 0.05) and in the AR- group (p < 0.01). Moreover, the eosinophil count was lower in the AR- group compared with the AR+ group (p < 0.05). Similarly, the number of EG2+ cells was greater in the AS group than in the AR group (p < 0.02) and the AR- group (p < 0.05). Moreover, the EG2+ cell count was lower in the AR- group than in the AR+ group (p < 0.05). The number of mast cells and basophils in the AS group was greater than that in the AR group (p < 0.05 and p < 0.01, respectively). Mast cells in sputum were tryptase-positive. Basophils were present in sputum from 23% of patients with AR and 53% of patients with asthma. There was a significant correlation between methacholine PD20 and eosinophils (p < 0.005) and mast cells (p < 0.02) but not with basophils in those patients showing a measurable methacholine PD20 (AR+ and AS groups). CONCLUSIONS: Inflammatory cells are present not only in the airways of patients with asthma but also in airways of patients with seasonal AR, even outside natural exposure. Moreover, we provide evidence for the presence of basophils in sputum of patients with asthma even during clinical remission. The presence of bronchial responsiveness is associated with an increase in the number of eosinophils and metachromatic cells. Our findings are consistent with the hypothesis that eosinophils, as well as mast cells, contribute to bronchial responsiveness not only in AS but also in seasonal AR.

Activity of erdosteine on mucociliary transport in patients affected by chronic bronchitis.

The influence of erdosteine (a mucomodulator endowed with mucolytic and antioxidant properties) on human mucociliary transport (MCT) was investigated in a double-blind placebo controlled study. Sixteen former smokers affected by chronic bronchitis, preselected for their mucociliary responsiveness to an inhaled beta 2-agonist, were divided into two groups (matched by number, sex, age and FEV1%) and orally treated with placebo or erdosteine (300 mg t.i.d.) for 8 days. Their MCT was assessed by the bronchofiberscopy technique just before starting the treatment and at the end of the treatment. The pretreatment mucus transport velocity in these patients was significantly decreased with respect to healthy subjects. The erdosteine treatment induced a significant improvement of MCT while placebo was inactive (mean % variation +/- SE against their baseline values being +60.4 +/- 18.4 and -3.0 +/- 5.9, respectively). This peculiar activity of erdosteine on mucus transport may be of clinical usefulness in chronic bronchitic patients and it can be added to beta 2-agonist to restore the decreased MCT.

[Localization of hydatid cysts in the left hemidiaphragm. Description of a case]. / La localizzazione all'emidiaframma sinistro della cisti idatidea. Descrizione di un caso.

The authors studied a 43-YR. old woman with a hydatid cyst, localized in the left diaphragm and extending into the left lung and the liver. De to difficulties in diagnosing the type, location, and extension of the lesion and its nonspecific symptoms, hydatid cysts are frequently not considered outside the endemic areas when formulating a differential diagnosis. Chest and abdominal CAT scanning permits a satisfactory definition of both the type of process and its topographical relationships. This permits the most appropriate surgical route to be chosen in performing a left thoracotomy in order to surgically afford the abdominal component of the cyst. This proved easy to remove, despite the existence of a tangle of adhesions, and had a favourable outcome, both immediately after surgery, and with long term follow-up.