Antonio Castagnaro

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.

Assessment of Breathlessness Perception by Borg Scale in Asthmatic Patients: Reproducibility and Applicability to Different Stimuli

In asthmatics, the score of bronchoconstriction-associated breathlessness at 20% fall in forced expiratory volume at first second (FEV1) evaluated on a Borg scale (PS20) is a tool successfully used to measure the perception of symptoms. This prospective laboratory study evaluated the applicability of PS20 to assess the breathlessness induced by ultrasonically nebulized distilled water (UNDW) and methacholine (M) and its reproducibility. Twenty-two mild and clinically stable asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated by linear interpolation of the last two points of the perception/fall in FEV1 curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did not differ and were respectively 1.82 ± 1.85 and 2.03 ± 1.86. They were significantly related (rs = 0.63; p<0.01) and the bias between PS20 UNDW and PS20 M was –0.21 with the limits of agreement ranging from –3.2 to 3.6. The intraclass correlation coefficient for repeated measurement of PS20 M was 0.82; the bias between the two measurements was 0.2 with the limits of agreement ranging from –2.8 to 3.2. All patients had a measurable breathlessness perception degree on a Borg scale during both distilled water challenges and methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness perception were also similar for both stimuli. In addition, PS20 showed a good reproducibility and this allows the serial evaluation of patients breathlessness perception by this technique in clinical settings and in the physiology laboratory.

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.

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.

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

PurposeAirway-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 methodsWe studied seven patients (two men, age range 36–69 years) with chronic asthma [forced expiratory volume in the first second (FEV1) 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 cmH2O by nasal insufflation with continuous positive airway pressure (nCPAP), both at baseline and after inhalation of 200 μg oxitropium bromide metered dose inhaler (MDI). External and lumen diameter (mm) of the right apical upper lobe bronchus were measured in all HRCT scans.ResultsIn asthmatics, 12 cmH2O 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 cmH2O 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 cmH2O 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 cmH2O but not of 6 cmH2O induced a significant change in lumen diameter (5.0±1.5 mm vs. 6,0±1.6 mm; p<0.05).ConclusionsOur 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.RiassuntoObiettivoNell’asma bronchiale il rimodellamento di parete può portare ad una riduzione della distensibilità delle vie aeree. Questo studio valuta il calibro di base e il grado di distensibilità delle vie aeree nei pazienti asmatici con l’impiego della TC ad alta risoluzione (HRCT).Materiali e metodiAbbiamo studiato 7 pazienti (2 maschi, range di età: 36–69 anni) con asma cronica in condizioni cliniche stabili (FEV1 range: 30%–87% del valore predetto; FEV1/FVC range: 48%–75% del valore predetto) e 6 controlli sani (3 maschi, range di età: 29–50 anni). In tutti i soggetti sono state effettuate scansioni HRCT a fine espirazione a riposo e durante ventilazione mediante cPAP con 6 e 12 cmH2O, sia in condizioni basali, sia dopo inalazione di 200 μg di oxitropio bromuro MDI. In tutte le scansioni HRCT sono stati misurati il diametro del lume e il diametro esterno del bronco segmentale apicale del lobo superiore di destra.RisultatiNei pazienti asmatici, l’insufflazione con la pressione di 12 cmH2O ha cambiato in modo significativo il diametro di base del lume (3,3±0,7 mm vs 3,8±0,6 mm; p<0.,01) e il diametro esterno (6,2±0,9 mm vs 6,7±0,8 mm; p<0,05) mentre nei controlli sani, l’insufflazione con la pressione di 6 cmH2O e di 12 cmH2O ha prodotto cambiamenti significativi a carico del diametro basale del lume (4,0±1,6 mm vs 4,8±1,6 mm e 4,7±1,7 mm; p<0,01). Nei pazienti asmatici, l’inalazione di oxitropio bromuro ha cambiato significativamente il diametro di base del lume (3,3±0,7 mm vs 4,4±0,6 mm; p<0,05) mentre l’insufflazione con la pressione di 6 o di 12 cmH2O non ha modificato nessun diametro bronchiale. Nei controlli sani l’inalazione di oxitropio bromuro ha modificato in modo significativo il diametro di base del lume (4,0±1,6 mm vs 5,0±1,5 mm; p<0,05). L’applicazione di una pressione di 12 cmH2O, ma non di 6 cmH2O, ha indotto un significativo cambiamento nel diametro del lume (5,0±1,5 mm vs 6,0±1,6 mm; p<0,05).ConclusioniI nostri risultati dimostrano che nei pazienti asmatici il grado di distensibilità delle vie aeree, misurato mediante HRCT, può essere diverso se comparato a quello dei controlli sani. La HRTC può fornire informazioni utili sulla distensibilità delle vie aeree.

Changes in lung function and respiratory muscle strength after sternotomy vs. laparotomy in patients without ventilatory limitation.

A relevant ventilatory defect occurs after sternotomy, a very common thoracic surgical opening. The mechanism of the ventilatory impairment is unclear. Moreover, until now, the effect of sternotomy on pulmonary gas exchange has scarcely been investigated. We evaluated the time-course up to recovery and changes in spirometry, maximum static inspiratory (PImax) and expiratory (PEmax) mouth pressures and pulmonary gas exchange in 6 patients after sternotomy and in 8 patients after laparotomy. All patients were free of cardiopulmonary diseases and had normal preoperative lung function. Sternotomy and laparotomy decreased forced vital capacity (FVC) by 67 and 49%, respectively. Moreover, the percent decreases in PImax, PEmax and PaO2 after sternotomy vs. laparotomy were respectively 54 vs. 57%, 54 vs. 60%, and 22.6 vs. 7.5% (p < 0.05). Following sternotomy, the percent decreases in FVC correlated with the percent decreases in PImax (p < 0.05) and PEmax (p < 0.01). The return to baseline values occurred after approximately 2 weeks. The present study shows that sternotomy can induce greater respiratory effects than laparotomy and suggests a relevant involvement of respiratory muscle weakness after surgical opening of the thorax. The study also supports the view that the evaluation of patient’s lung function before sternotomy can be clinically relevant.

The lung in immune-mediated disorder: rheumatoid arthritis.

Various pleuro-pulmonary abnormalities are known to complicate vascular collagen diseases, particularly, rheumatoid arthritis. Each component of the respiratory system is affected, either separately or in combination. Although most pulmonary complications appear in an established case of collagen vascular disease, in certain conditions, the lung disease precedes the more typical manifestation. While some complications are asymptomatic and tend to be resolved spontaneously (for e.g. pleuritis and rheumatoid nodules), others may cause severe or fatal conditions (interstitial pneumonia and constrictive bronchiolitis). The incidence of interstitial lung disease is increasing in vascular collagen disease. This may be mainly attributed to the increase use of invasive techniques such as bronchoscopy and video-assisted thoracoscopic surgery and in part due to the use of high resolution computed tomography, and functional pulmonary tests.

Pathophysiology of a Fall in Arterial Oxygen Saturation During Sputum Induction

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