Maria Bellia

Airway remodelling assessed by sputum and high-resolution computed tomography in asthma and COPD

It is not known whether sputum elastase, metalloproteinase (MMP)-9 and tissue-inhibitor metalloproteinase (TIMP)-1 are related to structural changes of the airways, as assessed by high-resolution computed tomography (HRCT) scan. The relationships between these markers and the magnitude of structural changes of the airways in asthma and chronic obstructive pulmonary disease (COPD) were assessed. Induced sputum and HRCT scan were performed in 30 asthmatics (14 mild and 16 severe) and in 12 patients with COPD. A greater extent of HRCT scan abnormalities was found in COPD than in severe and mild asthmatics. HRCT scan abnormalities correlated with the degree of airway obstruction in COPD and in severe asthma. HRCT scan abnormalities also correlated with the levels of sputum elastase both in COPD and in severe asthma. HRCT scan abnormalities were associated with sputum MMP-9/TIMP-1 ratio in mild asthma, severe asthma and COPD. In conclusion, this study demonstrates that sputum elastase and the metalloproteinase-9/tissue-inhibitor metalloproteinase-1 ratio are associated with the magnitude of high-resolution computed tomography scan abnormalities of the airways in asthma and chronic obstructive pulmonary disease, and suggests that the levels of these markers reflect the extent of structural changes of the airways.

HRCT and scleroderma: semiquantitative evaluation of lung damage and functional abnormalities

PurposeThis study sought to validate the Warrick score in the assessment of lung involvement in systemic sclerosis (SSc) and correlate the results with functional abnormalities. In addition, we propose the use of highresolution computed tomography (HRCT) indices of alveolitis and fibrosis to discriminate between different stages of the disease.Materials and methodsThirty-one patients with SSc (16 with the diffuse form and 15 with the limited form) underwent functional and HRCT evaluations of the lung. The semiquantitative evaluation of radiological involvement, as proposed by Warrick, provides a score for each lesion based on the severity and the extent of the pulmonary damage. In addition to the total score, indices for alveolitis and fibrosis were created. The association between each score and functional abnormalities was tested.ResultsThe total Warrick score was 16±7.7 [mean±standard deviation (SD)]. The total score correlated inversely with total lung capacity (TLC) (percentage of predicted TLC) (r=−0.38; p=0.04), diffusion lung capacity for carbon monoxide (DLCO) (percentage of predicted DLCO) (r=−0.43; p=0.02) and with forced expiratory volume in 1 second (FEV1) (percentage of predicted FEV1) (r=−0.36; p=0.05). The alveolitis and fibrosis indices were 1.9±1.1 and 14.2±7.4, respectively. The alveolitis index correlated significantly with percentage of predicted DLCO (r=−0.46; p=0.01) but not with percentage of predicted TLC (r=−0.28; p=0.13). The fibrosis index correlated both with percentage of predicted DLCO (r=−0.38; p=0.04) and with percentage of predicted TLC (r=−0.35; p=0.05).ConclusionsOur findings confirm the diagnostic role of HRCT in assessing the extent of lung damage in SSc. Furthermore, the two indices (alveolitis and fibrosis) provide new tools for evaluating the relationship between pulmonary involvement and systemic impairment in SSc.RiassuntoObiettivoScopo del lavoro è stato contribuire alla validazione del metodo del punteggio (score) radiologico di Warrick nella valutazione del danno polmonare nella sclerosi sistemica (ScS) e di correlare i risultati con le alterazioni della funzionalità respiratoria. Proponiamo inoltre l’introduzione di punteggi parziali relativi rispettivamente ad un indice di alveolite e di fibrosi per una migliore caratterizzazione delle diverse forme della malattia.Materiali e metodiTrentuno pazienti affetti da ScS, 16 da forma diffusa (dScS), 15 da forma limitata (lScS), sono stati sottoposti a valutazione respiratoria funzionale e radiologica tramite HRCT. La valutazione semiquantitativa della compromissione radiologica è stata effettuata mediante il metodo di Warrick, che attribuisce un punteggio alle varie lesioni secondo un criterio di gravità (score di severità del danno) e di estensione delle stesse alterazioni all’interno del parenchima polmonare (score di estensione del danno). Oltre allo score totale, sono stati arbitrariamente distinti un indice di “alveolite” e un indice di “fibrosi”. I punteggi ottenuti sono stati correlati ai risultati dei test di funzionalità respiratoria.RisultatiLo score totale di Warrick è risultato pari a 16±7,7 (media±DS). Lo score totale è risultato inversamente correlato con la capacità polmonare totale (TLC% del teorico) (r=−0,38 e p=0,04), con la diffusione al monossido di carbonio (DLCO% del teorico) (r=−0,43 e p=0,02), e con il FEV1% del teorico (r=−0,36 e p=0,05). L’indice di alveolite e l’indice di fibrosi sono risultati rispettivamente pari a 1,9±1,1 e 14,2±7,4. L’indice di alveolite si è dimostrato significativamente correlato alla DLCO% del teorico (r=−0,46, p=0,01) ma non alla TLC% del teorico (r=−0,28, p=0,13); al contrario, l’indice di fibrosi correlava significativamente sia con la DLCO% del teorico (r=−0,38, p=0,04) che con la TLC% del teorico (r=−0,35, p=0,05).ConclusioniI risultati del presente studio confermano il valore diagnostico dell’HRCT nel rappresentare il tipo e l’estensione del danno polmonare determinato dalla ScS. Inoltre, la suddivisione in punteggi parziali (alveolite e fibrosi) apre una ulteriore prospettiva di valutazione dei rapporti tra interessamento polmonare e compromissione sistemica.

The airway response to deep inspirations decreases with COPD severity and is associated with airway distensibility assessed by computed tomography

In patients with mild chronic obstructive pulmonary disease (COPD), the effect of deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend the airways. Fifteen subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-II: n = 7; GOLD stage III-IV: n = 8] underwent methacholine bronchoprovocation in the absence of DI, followed by DI. The effectiveness of DI was assessed by their ability to improve inspiratory vital capacity and forced expiratory volume in 1 s (FEV(1)). To evaluate airway distensibility, two sets of high-resolution computed tomography scans [at residual volume (RV) and at total lung capacity] were obtained before the challenge. In addition, mean parenchymal density was calculated on the high-resolution computed tomography scans. We found a strong correlation between the response to DI and baseline FEV(1) %predicted (r(2) = 0.70, P < 0.0001) or baseline FEV(1)/forced vital capacity (r(2) = 0.57, P = 0.001). RV %predicted and functional residual capacity %predicted correlated inversely (r(2) = 0.33, P = 0.02 and r(2) = 0.32, P = 0.03, respectively), and parenchymal density at RV correlated directly (r(2) = 0.30, P = 0.03), with the response to DI. Finally, the effect of DI correlated to the change in large airway area from RV to total lung capacity (r(2) = 0.44, P = 0.01). We conclude that loss of the effects of DI is strongly associated with COPD severity and speculate that the reduction in the effectiveness of DI is due to the failure to expand the lungs because of the hyperinflated state and/or the parenchymal damage that prevents distension of the airways with lung inflation.

Physical capacity in performing daily activities is reduced in scleroderma patients with early lung involvement.

Patients with systemic sclerosis (SSc) often complain reduced capacity at submaximal exercise; conversely, physical capacity in performing daily duties has never been measured in SSc. The aim of this study is to evaluate this performance and its correlates, in patients with SSc compared with healthy controls, in a free‐living setting.

Airway Distensibility by HRCT in Asthmatics and COPD with Comparable Airway Obstruction

Abstract Introduction: Decreased airway distensibility (AD) in response to deep inspirations, as assessed by HRCT, has been associated with the severity of asthma and COPD. Aims: The current study was designed to compare the magnitude of AD by HRCT in individuals with asthma and COPD with comparable degrees of bronchial obstruction, and to explore factors that may influence it. Results: We enrolled a total of 12 asthmatics (M/F:7/5) and 8 COPD (7/1) with comparable degree of bronchial obstruction (FEV1% predicted mean±SEM: 69.1 ± 5.2% and 61.2 ± 5.0%, respectively; p = 0.31). Each subject underwent chest HRCT at FRC and at TLC. A total of 701 airways (range 20 to 38 airway per subject; 2.0 to 23.1 mm in diameter) were analyzed. AD did not differ between asthmatics and COPD (mean ± SEM: 14 ± 3.5% and 17 ± 4.3%, respectively; p = 0.58). In asthmatics, AD was significantly associated with FEV1% predicted (r2 = 0.45, p = 0.018). We found a significant correlation between the change in lung volume and the change in AD by HRCT (r2 = 0.64, p = 0.002). In COPD, we found significant correlations between AD and the RV% predicted (r2 = 0.51, p = 0.046) and the RV/TLC (r2 = 0.68, p = 0.01). Conclusions: AD was primarily affected by the dynamic ability to change lung volumes in asthmatics, and by static lung volumes in COPD.

A 15-Year-Old Boy with Anterior Chest Pain, Progressive Dyspnea, and Subcutaneous Emphysema of the Neck

We describe the case of an adolescent who was admitted to the hospital because of sudden occurrence of chest pain, dyspnea and subcutaneous emphysema. On admission, physical examination revealed subcutaneous crepitations in the superior part of the rib cage, and auscultation of the chest showed widespread wheezing. The radiological assessment confirmed the diagnosis of pneumomediastinum and pneumothorax. A follow-up CT scan performed one week after the admission showed almost complete resolution of the radiological alterations. At the following visits, the patient was asymptomatic, but reported to have suffered from frequent episodes of rhinorrea, sneezing, nasal blockage, and sometimes, chest tightness, especially during exposure to pets and/or windy weather. Skin prick testing showed sensitivities to dermatophagoides pteronyssinus and farinae, grass pollen and dog dander. Spirometry documented significant improvement in lung function after short-acting bronchodilator, allowing for the diagnosis of asthma to be made. Although pneumomediastinum may be a complication of various respiratory diseases, including asthma, it has never been reported as the first presentation of underlying bronchial asthma. Herein, the physiopathological mechanisms, the diagnostic procedures and treatment of pneumomediastinum in asthma are discussed. We suggest that the diagnosis of asthma should be considered in the differential diagnosis of pneumomediastinum in adolescence.

Alterations of the beneficial effect of deep inspiration in scleroderma: relationships between lung function and imaging.

Background: It has been postulated that the beneficial effects of deep inspiration are dependent on the magnitude of airway distension by virtue of airway to parenchyma interdependence. Objective: This study was designed to examine whether the changes that occur in pulmonary fibrosis affect the beneficial effect of deep inspiration. Methods: Thirty-one subjects with scleroderma underwent lung volume and diffusion capacity assessment as well as high-resolution computed tomography. To assess the effect of deep inspiration, each subject underwent methacholine provocations in the absence of deep breaths. When the targeted change in lung function was achieved, subjects were asked to take 4 consecutive deep inspirations after which lung function measurements were repeated. The inspiratory vital capacity (IVC) was used as primary outcome. Results: Only 19 subjects attained the desired reduction in IVC in the absence of deep breaths. In those subjects, deep inspiration reversed the effect of methacholine on IVC by 48 ± 8.4%. The effect of deep inspiration correlated with DLCO% predicted (r = 0.55, p = 0.01), but not with high-resolution computed tomography abnormalities or baseline lung function measurements. When all subjects were considered, responsiveness to methacholine in the absence of deep inspiration was progressively lower with decreasing DLCO% predicted values (r = 0.51, p = 0.003). Conclusions: In systemic scleroderma, pulmonary abnormalities resulting in mild to moderate reduction in the diffusion capacity are associated with reduced ability of deep inspiration to reverse methacholine-induced early airway closure and bronchoconstriction. When diffusion capacity is severely affected, methacholine fails to produce obstructive airway changes.