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Background and objective: Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study. Methods: The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18–40 years and newly treated with ICS during 2005–2008, was followed from their first ICS dispensation until 2010. Discontinuation of treatment with ICS and starting oral corticosteroid therapy during follow-up were respectively regarded as proxies of poor persistence with asthma medication and asthma exacerbation (outcomes). A proportional hazards model was fitted to identify predictors of ICS discontinuation. Case-crossover and case-case-time-control designs and conditional logistic regressions were used to estimate the association between persistence with ICS and asthma exacerbation. Results: Cumulative incidences of discontinuation were 36%, 57% and 78% at 6 months, 1 year and 5 years, respectively. Predictors of poor persistence were female gender, use of antibiotics during follow-up, absence of use of short-acting beta-agonists prior to and after starting treatment with ICS and starting and maintaining ICS monotherapy during follow-up. The odds ratios of asthma exacerbation (and 95% confidence intervals) associated with ICS exposure during the current period, contrasted with exposure during the reference period, were 0.4 (0.2, 0.9) and 0.3 (0.1, 1.0) from case-crossover and case-case-time-control estimates, respectively. Conclusion: Persistence with ICS treatment in adults with asthma reduces the risk of exacerbation in the real-life setting.

Background In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. Methods We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. Results At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. Conclusions In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease., Background In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. Methods We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. Results At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. Conclusions In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.

During the past decades, a growing interest has been raised in evaluating nontuberculous mycobacteria (NTM) in patients with noncystic fibrosis bronchiectasis (NCFBE). This paper reviews several aspects of the correlations between NTM and NCFBE, including pathogenesis, radiological features, diagnosis, and management. Bronchiectasis and NTM lung disease are connected, but which one comes first is still an unresolved question. The rate of NTM lung disease in NCFBE varies through the studies, from 5% to 30%. The most frequent species isolated is MAC. NCFBE patients affected by NTM infection frequently present coinfections, including both other different NTM species and microorganisms, such as P. aeruginosa. Once a diagnosis of NTM disease has been reached, the initiation of therapy is not always mandatory. NTM species isolated, patients' conditions, and disease severity and its evolution should be considered. Risk factors for disease progression in NCFBE patients with NTM are low body mass index, cavitary disease, consolidations, and macrolide resistance at presentation.

Rationale: Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. Objectives: The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. Methods: We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Measurements and Main Results: Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P<0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Conclusions: Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.

Introduction: Delirium is common in critically ill patients and impact in-hospital mortality in patients with pneumonia. The aim of the study was to evaluate the prevalence of delirium symptoms during hospitalization in patients with severe pneumonia and their impact on one-year mortality. Methods: This was an observational, retrospective, cohort study of consecutive patients admitted to the respiratory high dependency unit of the San Gerardo University Hospital, Monza, Italy, between January 2009 and December 2012 with a diagnosis of severe pneumonia. A search through the charts looking for ten key words associated with delirium (confusion, disorientation, altered mental status, delirium, agitation, inappropriate behavior, mental status change, inattention, hallucination, lethargy) was performed by a multidisciplinary team. The primary endpoint was mortality at one-year follow-up. Secondary endpoint was in-hospital mortality. Results: A total of 172 patients were enrolled (78 % males; median age 75 years). At least one delirium symptom was detected in 53 patients (31 %) during hospitalization. The prevalence of delirium symptoms was higher among those who died during hospitalization vs. those who survived (44 vs. 27 %, p = 0.049, respectively). Seventy-one patients (46 %) died during the one-year follow-up. The prevalence of at least one delirium symptom was higher among those who died than those who survived during the one-year follow-up (39 vs. 21 %, p = 0.014, respectively). At the multivariable logistic regression analysis, after adjustment for age, comorbidities and severe sepsis, the presence of at least one delirium symptom during hospitalization was an independent predictor of one-year mortality (OR 2.35; 95 % CI 1.13–4.90; p = 0.023). Conclusions: Delirium symptoms are independent predictors of one-year mortality in hospitalized patients with severe pneumonia. Further studies should confirm our results using prospective methods of collecting data.

We present the results of bronchoalveolar lavage (BAL) performed in three patients with severe influenza A/H1N1 pneumonia complicated by acute respiratory distress syndrome (ARDS). Light microscopy analysis of BAL cytocentrifugates showed the presence of characteristic large, mononuclear, plasmoblastic/plasmocytoid-like cells never described before. Via transmission electron microscopy, these cells were classified as atypical type II pneumocytes and some of them showed cytoplasmic vesicles and inclusions. We concluded that plasmoblastic/plasmocytoid-like type II pneumocytes might represent a morphologic marker of A/H1N1 influenza virus infection as well as reparative cellular activation after diffuse alveolar damage.

To evaluate noninvasive ventilation (NIV) in diffuse interstitial lung diseases (DILD) patients with acute respiratory failure (ARF) according to baseline radiological patterns and the etiology of ARF

The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.

The case of an 87-year-old woman who falls at home and is admitted to the Emergency Department of an acute hospital with delirium exemplify a common situation that physicians face in their everyday clinical practice. We describe the typical context of frailty in which acute illnesses frequently present in frail elderly patients and, in particular, the relationship between comorbidity, disability and frailty. We also report the current knowledge about frailty theories and we focus on the "atypical" presentation of many acute illnesses. Major attention is devoted on delirium and on mobility impairment, two of the most common atypical symptoms of elderly frail subjects. Finally we describe the evidence on the comprehensive geriatric assessment, i.e., the method that is required to identify and understand the ultimate needs of elderly complex subjects.

Rationale: There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research. Objectives: This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI). Methods: Derivationof theBSI used data fromaprospective cohort study (Edinburgh, UK, 2008-2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253);Monza, Italy (n = 105); and Newcastle, UK (n = 126). Measurements and Main Results: Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 , 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74-0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84-0.91) for hospitalization, respectively. Therewas a clear difference in exacerbation frequency and quality of life using the St. George's Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P<0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88. Conclusions: The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacer

Background: Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.Methods: This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.Results: Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).Conclusions: The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.

Pneumonia is one of the main causes of morbidity and mortality in the elderly. The elderly population has exponentially increased in the last decades and the current epidemiological trends indicate that it is expected to further increase. Therefore, recognizing the special needs of older people is of paramount importance. In this review we address the main differences between elderly and adult patients with pneumonia. We focus on several aspects, including the atypical clinical presentation of pneumonia in the elderly, the methods to assess severity of illness, the appropriate setting of care, and the management of comorbidities. We also discuss how to approach the common complications of severe pneumonia, including acute respiratory failure and severe sepsis. Moreover, we debate whether or not elderly patients are at higher risk of infection due to multi-drug resistant pathogens and which risk factors should be considered when choosing the antibiotic therapy. We highlight the differences in the definition of clinical stability and treatment failure between adults and elderly patients. Finally, we review the main outcomes, preventive and supportive measures to be considered in elderly patients with pneumonia