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De Martino M.,University of Naples Federico II | Trotta A.,UOSC Immunologia Oncologica | Bruzzese D.,University of Naples Federico II | Cicchitto G.,Fisiopatologia Respiratoria | And 4 more authors.
Cytokine | Year: 2014

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p<0.001). Conversely, the proportion and absolute number of CD3+CD4+CD25highFoxp-3+ cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed. © 2014 Elsevier Ltd.


Melani A.S.,Fisiopatologia e Riabilitazione Respiratoria | Bonavia M.,Pneumologia | Cilenti V.,Fisiopatologia Respiratoria | Cinti C.,Pneumotisiatria | And 7 more authors.
Respiratory Medicine | Year: 2011

Proper inhaler technique is crucial for effective management of asthma and COPD. This multicentre, cross-sectional, observational study investigates the prevalence of inhaler mishandling in a large population of experienced patients referring to chest clinics; to analyze the variables associated with misuse and the relationship between inhaler handling and health-care resources use and disease control. We enrolled 1664 adult subjects (mean age 62 years) affected mostly by COPD (52%) and asthma (42%). Respectively, 843 and 1113 patients were using MDIs and DPIs at home; of the latter, the users of Aerolizer ®, Diskus®, HandiHaler® and Turbuhaler® were 82, 467, 505 and 361. We have a total of 2288 records of inhaler technique. Critical mistakes were widely distributed among users of all the inhalers, ranging from 12% for MDIs, 35% for Diskus ® and HandiHaler® and 44% for Turbuhaler ®. Independently of the inhaler, we found the strongest association between inhaler misuse and older age (p = 0.008), lower schooling (p = 0.001) and lack of instruction received for inhaler technique by health caregivers (p < 0.001). Inhaler misuse was associated with increased risk of hospitalization (p = 0.001), emergency room visits (p < 0.001), courses of oral steroids (p < 0.001) and antimicrobials (p < 0.001) and poor disease control evaluated as an ACT score for the asthmatics (p < 0.0001) and the whole population (p < 0.0001). We conclude that inhaler mishandling continues to be common in experienced outpatients referring to chest clinics and associated with increased unscheduled health-care resource use and poor clinical control. Instruction by health caregivers is the only modifiable factor useful for reducing inhaler mishandling. © 2010 Elsevier Ltd. All rights reserved.


Barisione G.,Fisiopatologia Respiratoria | Bacigalupo A.,Ematologia 2 | Brusasco C.,University of Genoa | Scanarotti C.,University of Genoa | And 6 more authors.
Respiratory Physiology and Neurobiology | Year: 2014

Lung diffusing capacity for CO (DLCO) is compromised in haematopoietic stem-cell transplantation (HSCT) recipients. We derived alveolar-capillary membrane conductance (DM,CO) and pulmonary capillary volume (VC) from DLCO and diffusing capacity for NO (DLNO). Forty patients were studied before and 6 weeks after HSCT. Before HSCT, DLNO and DLCO were significantly lower than in 30 healthy controls. DM,CO was ~40% lower in patients than in controls (p<0.001), whereas VC did not differ significantly. After HSCT, DLNO and DM,CO further decreased, the latter by ~22% from before HSCT (p<0.01) while VC did not change significantly. Lung density, serum CRP and reactive oxygen metabolites were significantly increased, with the latter being correlated (R2=0.71, p<0.001) with the decrement in DLNO. We conclude that DLNO and, to a lesser extent, DLCO are compromised before HSCT mainly due to a DM,CO reduction. A further reduction of DM,CO without VC loss occurs after HSCT, possibly related to development of oedema, or interstitial fibrosis, or both. © 2014 Elsevier B.V.


Ambrosino N.,U.O. Pneumologia e Terapia Intensiva Respiratoria | Ambrosino N.,Volterra | Confalonieri M.,Science Pneumologia | Crescimanno G.,Cervello | And 2 more authors.
Respiratory Medicine | Year: 2013

Respiratory failure is an unavoidable event in the natural history of some neuromuscular diseases, while appearing very infrequently in others. In some cases, such as Pompe disease, respiratory failure progresses more rapidly than motor impairment, sometimes being the onset event. Home mechanical ventilation improves survival and quality of life of these patients, with a reduction in healthcare costs. Therefore, pulmonologists must improve their skills in order to play a more relevant role in the care of these patients. The aim of this statement is to provide pulmonologists with some simple information in order for them to fulfil their role of primary caregiver, enabling appropriate and rapid diagnosis and treatment. © 2013.


Barisione G.,Fisiopatologia Respiratoria | Pompilio P.P.,Polytechnic of Milan | Bacigalupo A.,Ematologia 2 | Brusasco C.,University of Genoa | And 6 more authors.
Respiratory Physiology and Neurobiology | Year: 2012

The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (Grs) at 5, 11 and 19Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (Grs5) were related to changes in lung volume (ΔGrs5/ΔVL) to estimate airway distensibility. Grs at FRC showed a slight but significant increase at all forcing frequencies by approximately 12-16%. TLC decreased after HSCT whereas the ΔGrs5/ΔVL ratio became higher after than before HSCT and was positively correlated (R2=0.87) with lung tissue density determined by quantitative CT scanning.We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT. © 2012 Elsevier B.V.


PubMed | Instituto Fondazione Renato Piatti, Divisione di Pneumologia, Centro anti fumo, Fisiopatologia Respiratoria and 6 more.
Type: | Journal: Respiratory care | Year: 2016

Regardless of the device used, many patients have difficulty maintaining proper inhaler technique over time. Repeated education from caregivers is required to ensure persistence of correct inhaler technique, but no information is available to evaluate the time required to rectify inhaler errors in experienced users with a baseline faulty technique and whether this time of re-education to restore inhaler mastery can differ between devices.This was a multi-center, single-visit, open-label, cross-sectional study in a large group of 981 experienced adult subjects (mean SD age 64 15 y), mainly suffering from COPD and asthma, who showed faulty inhaler technique at a follow-up visit in chest clinics. These subjects received face-to-face practical education from trained caregivers until proper inhaler use could be demonstrated, and the time of instruction was recorded.The mean times (95% CIs) in minutes of instruction required for rectifying misuse and demonstrating inhaler mastery were 5.0 (3.6-6.4) min for the Diskus (n = 199), 5.3 (3.7-6.8) min for the HandiHaler (n = 219), 8.1 (5.6-10.5) min for the metered-dose inhaler (MDI) (n = 532), and 6.0 (5.0-7.0) min for the Turbuhaler (n = 169). The time to demonstrate good inhaler use for MDIs was higher (P < .05) than for all dry powder inhalers (DPIs). Between the DPIs, only the HandiHaler required more time for achieving mastery than the Diskus (P = .005). The variables associated with increasing time for correcting inhaler errors were an older age (0.05 min/y, 95% CI 0.03-0.07), a lower level of education (0.4 min/schooling level, 95% CI 0.7-0.1), and no reported previous instruction in inhaler use (1.96 min, 95% CI 1.35-2.58).In experienced subjects with baseline faulty inhaler use, the mean time of education required to achieve and demonstrate mastery with DPIs was lower than with MDIs.


PubMed | Allergologia e Fisiopatologia Respiratoria, Fisiopatologia Respiratoria, University of Genoa, Ematologia 2 and Radiologia
Type: | Journal: Respiratory physiology & neurobiology | Year: 2014

Lung diffusing capacity for CO (DLCO) is compromised in haematopoietic stem-cell transplantation (HSCT) recipients. We derived alveolar-capillary membrane conductance (DM,CO) and pulmonary capillary volume (VC) from DLCO and diffusing capacity for NO (DLNO). Forty patients were studied before and 6 weeks after HSCT. Before HSCT, DLNO and DLCO were significantly lower than in 30 healthy controls. DM,CO was 40% lower in patients than in controls (p<0.001), whereas VC did not differ significantly. After HSCT, DLNO and DM,CO further decreased, the latter by 22% from before HSCT (p<0.01) while VC did not change significantly. Lung density, serum CRP and reactive oxygen metabolites were significantly increased, with the latter being correlated (R2=0.71, p<0.001) with the decrement in DLNO. We conclude that DLNO and, to a lesser extent, DLCO are compromised before HSCT mainly due to a DM,CO reduction. A further reduction of DM,CO without VC loss occurs after HSCT, possibly related to development of oedema, or interstitial fibrosis, or both.


The sleep correlated respiratory disturbances are an emergent sanitary problem and the obesity is also an increasing disease in west-countries. Because of the majority of patients with OSAS are obese and OSAS is the prevalent respiratory disturbance in the dedicated surgery, in the last years there is an increasing request of diagnosis and therapy of this disease. Epidemiologic data, different therapies indications, therapeutic ventilatory approach, more frequent therapy of severe OSAS, and its effects are described. Finally, is reported the economic aspect involving by the ventilatory therapy causing a great cost requiring a correct follow-up.


Ambrosino N.,U.O. Pneumologia e Terapia | Ambrosino N.,Volterra | Confalonieri M.,Science Pneumologia | Crescimanno G.,Cervello | And 2 more authors.
Rassegna di Patologia dell'Apparato Respiratorio | Year: 2012

Respiratory failure is an unavoidable or very frequent event in the natural history of some neuromuscular diseases, whereas it appears very unfrequently in others. In some cases, like Pompe disease, respiratory failure shows a more rapid worsening compared to motor impairment, sometimes being the onset event. The most frequent respiratory onset manifestation is exercise breathlessness, frequently associated to a history of lung infections. Nevertheless these patients may show a physiological picture of chronic respiratory insufficiency. Home mechanical ventilation improves survival and quality of life of these patients, with a reduction in health care costs. As a consequence pulmonologists must perform a more relevant role in the care of these patients and they must increase their skills for such a task. In Pompe disease mechanical ventilation is started during an episode of Acute Respiratory Failure (ARF) without any previous lung function tests: as a consequence these patients require more frequent physiological evaluations to avoid potentially fatal exacerbations. Therefore a collaboration between pulmonologist and neurologist is mandatory. Respiratory follow-up is aimed to early diagnosis and treatment of respiratory complications. It may differ according to different diagnosis and disease stage. The specific interest for adult onset Pompe disease relies on the aivailability of enzimatic therapy which has been shown to be effective in slowing disease progression. The aim of this statement is to give pulmonologists some simple information in order they can fulfil their role of "main caregiver" with appropriate and quick diagnosis and treatment.


PubMed | Fisiopatologia Respiratoria
Type: Journal Article | Journal: Respiratory physiology & neurobiology | Year: 2012

The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (G(rs)) at 5, 11 and 19 Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (G(rs5)) were related to changes in lung volume (G(rs5)/V(L)) to estimate airway distensibility. G(rs) at FRC showed a slight but significant increase at all forcing frequencies by approximately 12-16%. TLC decreased after HSCT whereas the G(rs5)/V(L) ratio became higher after than before HSCT and was positively correlated (R2=0.87) with lung tissue density determined by quantitative CT scanning. We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT.

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