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Acute respiratory failure (ARF) is a sudden failure of the respiratory system to ensure adequate gas exchanges. Numerous clinical conditions may cause ARF, including pneumonia, obstructive lung diseases (e.g., asthma), restrictive diseases such as neuromuscular diseases (e.g., spinal muscular atrophy and muscular dystrophy), and albeit rarely, interstitial lung diseases. Children, especially infants, may be more vulnerable to ARF than adults due to anatomical and physiological features of the respiratory system. Assessing respiratory impairment in the pediatric population is particularly challenging as children frequently present difficulties in reporting symptoms and due to compliance and cooperation in diagnostic tests. The evaluation of clinical and anamnestic aspects represents the cornerstone of ARF diagnosis: first level exams (e.g., arterial blood gas analysis) confirm and evaluate the severity of the ARF and second level exams help to uncover the underlying cause. Prompt management is critical, with supplemental oxygen, mechanical ventilation, and the treatment of the underlying problem. The aim of this review is to provide a comprehensive summary of the current state of the art in diagnosing pediatric ARF, with a focus on pathophysiology, novel imaging applications, and new perspectives, such as biomarkers and artificial intelligence.

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

Background: There is limited information available on fast and safe bedside tools that could help clinicians establish whether the pathological process underlying cases of wheezing is due to asthmatic exacerbation, asthmatic bronchitis, or pneumonia. The study's aim was to characterize Lung Ultrasound (LUS) in school-aged children with wheezing and evaluate its use for their follow-up treatment., Materials and Methods: We carried out a cross-sectional study involving 68 consecutive outpatients (mean age 9.9 years) with wheezing and suggestive signs of an acute respiratory infection. An expert sonographer, blinded to all subject characteristics, clinical course, and the study pediatrician's diagnosis, performed an LUS after spirometry and before BDT. The severity of acute respiratory symptoms was determined using the Pediatric Respiratory Assessment Measure (PRAM) score., Results: The LUS was positive in 38.2% (26/68) of patients [12 (46.1%) with multiple B-lines, 24 (92.3%) with consolidation, and 22 (84.6%) with pleural abnormalities]. In patients with pneumonia, asthmatic bronchitis, and asthma, the percentages of those patients with a positive LUS were 100%, 57.7%, and 0%, respectively. Of note, patients with a positive LUS were associated with an increased need for hospital admission (30.8% vs. 2.4%, p  = 0.001), administration of oxygen therapy (14.6% vs. 0%, p  = 0.009), oral corticosteroids (84.6% vs. 19.0%, p  < 0.001), and antibiotics (88.5% vs. 11.9%, p  < 0.001); and a higher median value of PRAM score (4.0 (2.0-7.0) vs. 2.0 (1.0-5.0); p  < 0.001)., Conclusions: Our findings would suggest the use of LUS as a safe and cheap tool used by clinicians to define the diagnosis of school-aged children with wheezing of unknown causes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Attanasi, Sferrazza Papa, Porreca, Sferrazza Papa, Di Filippo, Piloni, Dodi, Sansone, Di Pillo and Chiarelli.)

Background: Clinical and scientific evidence has shown that a range of long-lasting symptoms can persist in the post-virological period. However, little is known about the psychological sequelae of patients hospitalized for coronavirus disease 2019 (COVID-19). Objective: This study aims to assess the prevalence of anxiety-depressive symptoms, post-traumatic stress disorder (PTSD), and post-traumatic growth among patients hospitalized for COVID-19 during the first wave of the pandemic 6 months after discharge, and to identify sociodemographic and clinical factors associated with psychological outcomes. Method: This cross-sectional cohort study enrolled recovered COVID-19 patients during a multidisciplinary follow-up screening. At 6 months post-discharge, participants underwent a remote assessment with the Mini-International Neuropsychiatric Interview Plus and completed the Hospital Anxiety and Depression Scale, PTSD Checklist for DSM-5, and Post-Traumatic Growth Inventory. Descriptive and regression analyses were conducted. Results: The sample was composed of 100 patients, mainly males (72%), with a mean ±  SD age of 58.7 ± 11.8 years. Regarding psychological symptoms, 34% and 24% of patients, respectively, reported anxiety and depression over the clinical threshold, and 20% met the criteria for a possible PTSD diagnosis. Psychological symptoms were associated with the presence of a mood disorder in the patient's clinical history and having received a psychological consultation after discharge. Post-traumatic growth was associated with younger age and having received a psychological consultation after discharge. Conclusions: A high prevalence of anxiety and depressive symptoms, potentially indicative for a mood or anxiety disorder, and PTSD was confirmed among COVID-19 survivors after 6 months. Anxiety and depressive symptoms and PTSD were associated with a previous diagnosis of a mood disorder and having received psychological consultation. Post-traumatic growth was associated with younger age and having received psychological consultation. Tailored psychological interventions could help to elaborate the psychological suffering and foster post-traumatic growth after a traumatic experience such as COVID-19 hospitalization., Highlights: A high prevalence of psychological symptoms has been observed among COVID-19 survivors 6 months after hospitalization.Tailored psychological interventions could help to contain the psychological sequelae and facilitate post-traumatic growth., Competing Interests: No potential conflict of interest was reported by the authors., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The best noninvasive respiratory strategy in patients with Coronavirus Disease 2019 (COVID-19) pneumonia is still discussed. We aimed at assessing the rate of endotracheal intubation (ETI) in patients treated with continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) if CPAP failed. Secondary outcomes were in-hospital mortality and in-hospital length of stay (LOS). A retrospective, observational, multicenter study was conducted in intermediate-high dependency respiratory units of two Italian university hospitals. Consecutive patients with COVID-19 treated with CPAP were enrolled. Thoraco-abdominal asynchrony or hemodynamic instability led to ETI. Patients showing SpO 2 ≤ 94%, respiratory rate ≥ 30 bpm or accessory muscle activation on CPAP received NIV. Respiratory distress and desaturation despite NIV eventually led to ETI. 156 patients were included. The overall rate of ETI was 30%, mortality 18% and median LOS 24 (17-32) days. Among patients that failed CPAP ( n = 63), 28% were intubated, while the remaining 72% received NIV, of which 65% were intubated. Patients intubated after CPAP showed lower baseline PaO 2 /FiO 2 , lower lymphocyte counts and higher D-dimer values compared with patients intubated after CPAP + NIV. Mortality was 22% with CPAP + ETI, and 20% with CPAP + NIV + ETI. In the case of CPAP failure, a NIV trial appears feasible, does not deteriorate respiratory status and may reduce the need for ETI in COVID-19 patients.

Respiratory infection diseases are among the major causes of morbidity and mortality in children. Diagnosis is focused on clinical presentation, yet signs and symptoms are not specific and there is a need for new non-radiating diagnostic tools. Among these, lung ultrasound (LUS) has recently been included in point-of-care protocols showing interesting results. In comparison to other imaging techniques, such as chest X-ray and computed tomography, ultrasonography does not use ionizing radiations. Therefore, it is particularly suitable for clinical follow-up of paediatric patients. LUS requires only 5-10 min and allows physicians to make quick decisions about the patient's management. Nowadays, LUS has become an early diagnostic tool to detect pneumonia during the COVID-19 pandemic. In this narrative review, we show the most recent scientific literature about advantages and limits of LUS performance in children. Furthermore, we discuss the major paediatric indications separately, with a paragraph fully dedicated to COVID-19. Finally, we mention potential future perspectives about LUS application in paediatric respiratory diseases.

Objective: To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs., Design: Interventional, before-after study., Setting: A neurorehabilitation inpatient and outpatient center., Participants: Fifteen consecutive adult patients affected by neuromuscular diseases (N=15)., Interventions: AS treatment., Main Outcome Measures: Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R 5-19 ) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS., Results: Before AS, Borg score was significantly related to R 5-19 (r 2 0.46, P<.05) but not to VC % predicted, SNIP % predicted, and time since symptom onset. After AS, average Borg score gradually decreased (P=.005), whereas inspiratory flow resistance at 5 Hz, R 5-19, and inspiratory reactance at 5 Hz tended to improve, despite not reaching statistical significance. The decrease in dyspnea at 60 and 120 minutes after AS significantly correlated with baseline R 5-19 (r 2 0.49, P<.01 and r 2 0.29, P<.05, respectively), but not with VC % predicted, SNIP % predicted, time since symptom onset, and clinical severity score for patients affected by amyotrophic lateral sclerosis., Conclusions: These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea., (Copyright © 2021. Published by Elsevier Inc.)

Discriminating between cardiac and pulmonary dyspnea is essential for patients' management. We investigated the feasibility and ability of forced oscillation techniques (FOT) in distinguishing between acute exacerbation of COPD (AECOPD), and acute decompensated heart failure (ADHF) in a clinical emergency setting. We enrolled 49 patients admitted to the emergency department (ED) for dyspnea and acute respiratory failure for AECOPD, or ADHF, and 11 healthy subjects. All patients were able to perform bedside FOT measurement. Patients with AECOPD showed a significantly higher inspiratory resistance at 5 Hz, Xrs 5 (179% of predicted, interquartile range, IQR 94-224 vs. 100 IQR 67-149; p = 0.019), and a higher inspiratory reactance at 5 Hz (151%, IQR 74-231 vs. 57 IQR 49-99; p = 0.005) than patients with ADHF. Moreover, AECOPD showed higher heterogeneity of ventilation (respiratory system resistance difference at 5 and 19 Hz, Rrs 5-19 : 1.49 cmH 2 O/(L/s), IQR 1.03-2.16 vs. 0.44 IQR 0.22-0.76; p = 0.030), and a higher percentage of flow limited breaths compared to ADHF (10%, IQR 0-100 vs. 0 IQR 0-12; p = 0.030). FOT, which resulted in a suitable tool to be used in the ED setting, has the ability to identify distinct mechanical properties of the respiratory system in AECOPD and ADHF.

Background: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak., Methods: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020., Results: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015)., Conclusions: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.

Background: Deterioration of vital capacity (VC) in amyotrophic lateral sclerosis (ALS) signifies disease progression and indicates need for non-invasive ventilation. Weak facial muscles consequent to ALS, with resulting poor mouth seal, may interfere with the accuracy of VC measurements., Objectives: To determine whether different interfaces affect VC measurements in ALS patients and whether the interface yielding the largest VC produces an even higher VC when re-measured after one week (learning effect). To explore the relationship between optimal interface VC and sniff nasal pressure (SNIP), a measurement of global inspiratory muscle strength., Methods: Thirty-five patients (17 bulbar and 18 spinal ALS) were studied. Three interfaces (rigid-cylindrical, flanged, oronasal mask) were tested. One week after the first visit, VC was recorded using the optimal interface. SNIP recordings were also obtained., Results: In the bulbar ALS group, median (interquartile range) VC with the flanged mouthpiece was 8.4% (3.9-15.5) larger than with the cylindrical mouthpiece (p < 0.001). VC values with oronasal mask were intermediate to VC with the other two interfaces. In spinal ALS, flanged mouthpiece VC was 4.6% (2.3-7.5) larger than with oronasal mask (p < 0.0006). The latter was 4.5% (0.6-5.2) smaller than with the cylindrical mouthpiece (p = 0.002). In both groups, VC during the second visit was greater than during the first visit (p < 0.025). SNIPs were logarithmically related to VC values recorded with the flanged mouthpiece., Conclusion: A flanged mouthpiece yields the largest values of VC in patients with bulbar and spinal ALS., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided., Competing Interests: Conflict of interest: A.M. D'Arrigo has nothing to disclose. Conflict of interest: S. Floro has nothing to disclose. Conflict of interest: F. Bartesaghi has nothing to disclose. Conflict of interest: C. Casellato has nothing to disclose. Conflict of interest: G.F Sferrazza Papa has nothing to disclose. Conflict of interest: S. Centanni has nothing to disclose. Conflict of interest: A. Priori has nothing to disclose. Conflict of interest: T. Bocci has nothing to disclose., (Copyright ©ERS 2020.)

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease that is of great global public health concern., Objective: We explored the clinical management of inpatients with COVID-19 in Italy., Methods: A self-administered survey was sent by email to Italian physicians caring for adult patients with COVID-19. A panel of experts was selected according to their clinical curricula and their responses were analyzed., Results: A total of 1,215 physicians completed the survey questionnaire (17.4% response rate). Of these, 188 (15.5%) were COVID-19 experts. Chest computed tomography was the most used method to detect and monitor COVID-19 pneumonia. Most of the experts managed acute respiratory failure with CPAP (56.4%), high flow nasal cannula (18.6%), and non-invasive mechanical ventilation (8%), while an intensivist referral for early intubation was requested in 17% of the cases. Hydroxychloroquine was prescribed as an antiviral in 90% of cases, both as monotherapy (11.7%), and combined with protease inhibitors (43.6%) or azithromycin (36.2%). The experts unanimously prescribed low-molecular-weight heparin to patients with severe COVID-19 pneumonia, and half of them (51.6%) used a dose higher than standard. The respiratory burden in patients who survived the acute phase was estimated as relevant in 28.2% of the cases, modest in 39.4%, and negligible in 9%., Conclusions: In our survey some major topics, such as the role of non-invasive respiratory support and drug treatments, show disagreement between experts, likely reflecting the absence of high-quality evidence studies. Considering the significant respiratory sequelae reported following COVID-19, proper respiratory and physical therapy programs should be promptly made available., (© 2020 S. Karger AG, Basel.)

Introduction: Thoracic ultrasound is accurate in the diagnosis of a wide range of respiratory diseases. Yet the extent of its use is unknown. Through a national survey, we aimed to explore the clinical use of thoracic ultrasound and the barriers to the diffusion of the technique in Italy., Methods: Accademia di Ecografia Toracica (AdET) developed a self-administered survey which was sent by email to Italian pulmonologists via national scientific societies and networks., Results: Of the 2010 physicians invited, 514 completed the survey (26% response rate). According to 99% of responders, thoracic ultrasound had a relevant clinical role. Seventy-nine percent of the responders used thoracic ultrasound at least once a month. The main settings were: 53% pulmonology ward, 15% outpatient clinic, 15% interventional pulmonology room, 10% internal medicine ward, 4% respiratory intensive care units, and 9% other. Thoracic ultrasound was primarily used: (1) with both diagnostic and interventional aims (72%), (2) as diagnostic imaging (17%), and (3) as guidance for interventional procedures (11%). The main clinical applications were: (1) diagnosis and management of pleural effusion, (2) pneumothorax, (3) pneumonia, (4) cardiac failure, and (5) acute dyspnea. Twenty-one percent of the responders do not use thoracic ultrasound. The main reported bar-riers were: (1) availability of an ultrasound system (52%), (2) lack of protected time and training (22%), and (3) use of the technique by other specialists (15%)., Conclusion: Thoracic ultrasound is widely used by Italian pulmonologists and considered a clinically relevant tool. The availability of dedicated ultrasound systems seems to be a major limit of the use of the technique., (© 2020 S. Karger AG, Basel.)

Objectives: Lung CT is the reference imaging technique for acute respiratory distress syndrome, but requires transportation outside the intensive care and x-ray exposure. Lung ultrasound is a promising, inexpensive, radiation-free, tool for bedside imaging. Aim of the present study was to compare the global and regional diagnostic accuracy of lung ultrasound and CT scan., Design: A prospective, observational study., Setting: Intensive care and radiology departments of a University hospital., Patients: Thirty-two sedated, paralyzed acute respiratory distress syndrome patients (age 65 ± 14 yr, body mass index 25.9 ± 6.5 kg/m, and PaO2/FIO2 139 ± 47)., Interventions: Lung CT scan and lung ultrasound were performed at positive end-expiratory pressure 5 cm H2O. A standardized assessment of six regions per hemithorax was used; each region was classified for the presence of normal aeration, alveolar-interstitial syndrome, consolidation, and pleural effusion. Agreement between the two techniques was calculated, and diagnostic variables were assessed for lung ultrasound using lung CT as a reference., Measurements and Main Results: Global agreement between lung ultrasound and CT ranged from 0.640 (0.391-0.889) to 0.934 (0.605-1.000) and was on average 0.775 (0.577-0.973). The overall sensitivity and specificity of lung ultrasound ranged from 82.7% to 92.3% and from 90.2% to 98.6%, respectively. Similar results were found with regional analysis. The diagnostic accuracy of lung ultrasound was significantly higher when those patterns not reaching the pleural surface were excluded (area under the receiver operating characteristic curve: alveolar-interstitial syndrome 0.854 [0.821-0.887] vs 0.903 [0.852-0.954]; p = 0.049 and consolidation 0.851 [0.818-0.884] vs 0.896 [0.862-0.929]; p = 0.044)., Conclusions: Lung ultrasound is a reproducible, sensitive, and specific tool, which allows for bedside detections of the morphologic patterns in acute respiratory distress syndrome. The presence of deep lung alterations may impact the diagnostic performance of this technique.

Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other., Competing Interests: Conflict of interest: D. Chiumello has nothing to disclose. Conflict of interest: G.F. Sferrazza Papa has nothing to disclose. Conflict of interest: A. Artigas reports grants from Grifols, Fisher & Paykel, Fundacion Areces and Instituto Carlos III, outside the submitted work. Conflict of interest: B. Bouhemad has nothing to disclose. Conflict of interest: A. Grgic reports personal fees from MSD, Boehringer Ingelheim, Roche and Bayer Vital, outside the submitted work. Conflict of interest: L. Heunks reports personal fees for travel and lecturing from Maquet critical care, and grants from Ventfree and Orionpharma, outside the submitted work. Conflict of interest: K. Markstaller has nothing to disclose. Conflict of interest: G.M. Pellegrino has nothing to disclose. Conflict of interest: L. Pisani has nothing to disclose. Conflict of interest: D. Rigau works as a methodologist for the ERS. Conflict of interest: M.J. Schultz has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: P. Spieth has nothing to disclose. Conflict of interest: M. Zompatori has nothing to disclose. Conflict of interest: P. Navalesi has nothing to disclose., (Copyright ©ERS 2019.)

Interstitial lung diseases (ILDs) may be complicated by chronic respiratory failure (CRF), especially in the advanced stages. Aim of this narrative review is to evaluate the current evidence in management of CRF in ILDs. Many physiological mechanisms underlie CRF in ILDs, including lung restriction, ventilation/perfusion mismatch, impaired diffusion capacity and pulmonary vascular damage. Intermittent exertional hypoxemia is often the initial sign of CRF, evolving, as ILD progresses, into continuous hypoxemia. In the majority of the cases, the development of CRF is secondary to the worsening of the underlying disease; however, associated comorbidities may also play a role. When managing CRF in ILDs, the need for pulmonary rehabilitation, the referral to lung transplant centers and palliative care should be assessed and, if necessary, promptly offered. Long-term oxygen therapy is commonly prescribed in case of resting or exertional hypoxemia with the purpose to decrease dyspnea and improve exercise tolerance. High-Flow Nasal Cannula oxygen therapy may be used as an alternative to conventional oxygen therapy for ILD patients with severe hypoxemia requiring both high flows and high oxygen concentrations. Non-Invasive Ventilation may be used in the chronic setting for palliation of end-stage ILD patients, although the evidence to support this application is very limited., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In amyotrophic lateral sclerosis (ALS), respiratory muscle weakness leads to respiratory failure and death. Non-invasive positive pressure ventilation (NIPPV) appears to reduce lung function decline, thus improving survival and quality-of-life of patients affected by the disease. Unfortunately, clinical features and timing to start NIPPV are not well defined. Starting from recent findings, we examine established and novel tests of respiratory muscle function that could help clinicians decide whether and when to start NIPPV in ALS. Non-invasive tests estimate the function of inspiratory, expiratory, and bulbar muscles, whereas clinical examination allows to assess the overall neurologic and respiratory symptoms and general conditions. Most of the studies recommend that together with a thorough clinical evaluation of the patient according to current guidelines, vital capacity, maximal static and sniff nasal inspiratory pressures, maximal static expiratory pressures and peak cough expiratory flow, and nocturnal pulse oximetry be measured. A sound understanding of physiology can guide the physician also through the current armamentarium for additional supportive treatments for ALS, such as symptomatic drugs and new treatments to manage sialorrhea and thickened saliva, cough assistance, air stacking, and physiotherapy. In conclusion, careful clinical and functional evaluation of respiratory function and patient's preference are key determinants to decide "when" and "to whom" respiratory treatments can be provided.

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs., Methods: A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017)., Results: In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF., Conclusions: Despite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients' management, possibly leading to improved outcomes. However, further studies are warranted.

Objectives: Point-of-care lung sonography has theoretical usefulness in numerous diseases; however clinical indications and the impact of this technique have not been fully investigated. We aimed to describe the current use of point-of-care lung sonography., Methods: A 2-year prospective observational study was performed by pulmonologists in an Italian university hospital. Techniques, indications, consequences of lung sonography, and barriers to the examination were analyzed., Results: A total of 1150 lung sonographic examinations were performed on 951 patients. The most common indications were diagnosis and follow-up of pleural effusion in 361 cases (31%), evaluation of lung consolidation (322 [28%]), acute heart failure (195 [17%]), guide to pleural procedures (117 [10%]), pneumothorax (54 [5%]) and acute exacerbations of chronic obstructive pulmonary disease (30 [3%]). The mean duration of the examination ± SD was 6 ± 4 minutes. The transducers most frequently used were convex (746 [65%]) and linear (161 [14%]), whereas in 205 examinations (18%), both transducers were used. According to the judgment of the caring clinician, 51% of the examinations were clinically relevant., Conclusions: Point-of-care lung sonography performed by pulmonologists is quick and feasible and could be widely used for different clinical indications with a potentially high clinical impact. The widespread use of this technique may have a relevant clinical impact in several indications., (© 2017 by the American Institute of Ultrasound in Medicine.)

Severe bronchial asthma affects at least 5% of the asthmatic population and remains a clinical challenge. Data from the UK National Registry for Severe Asthma suggest that dedicated centers may improve asthma control, quality of life, reduce healthcare use and oral steroid burden. A multidisciplinary approach through complete lung function evaluation, optimization of adherence to treatment and immunological characterization are key issues to improve patients' care. In this paper, we provide an overview of the challenges of managing patients with severe asthma and the role of dedicated services.

Background: The need for additional research on symptomatic smokers with normal spirometry has been recently emphasized. Albeit not meeting criteria for Chronic obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may experience activity limitation, evidence of airway disease, and exacerbations. We, therefore, evaluated whether symptomatic smokers with borderline spirometry (post-bronchodilator FEV 1 /FVC ratio between 5th to 20th percentile of predicted values) have pulmonary function abnormalities at rest and ventilatory constraints during exercise., Methods: 48 subjects (aged 60 ± 8 years, mean ± SD, 73% males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise testing (CPET), body plethysmography, nitrogen single-breath washout test (N 2 SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation technique (FOT)., Results: Compared to healthy subjects, symptomatic smokers showed: 1) reduced breathing reserve (36 ± 17 vs. 49 ± 12%, P = 0.050); 2) exercise induced dynamic hyperinflation (-0.20 ± 0.17 vs. -0.03 ± 0.21 L, P = 0.043); 3) higher residual volume (158 ± 22 vs. 112 ± 22%, P < 0.001); 4) phase 3 slope at N 2 SBW (4.7 ± 2.1 vs. 1.4 ± 0.6%, P < 0.001); 5) no significant differences in DLCO and FOT results., Conclusions: In smokers with borderline spirometry, CPET and second-line pulmonary function tests may detect obstructive pattern. These subjects should be referred for second line testing, to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms. Whether the natural history of these patients is similar to COPD, and they deserve a similar therapeutic approach is worth investigating., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Lung and venous ultrasound are bedside diagnostic tools increasingly used in the early diagnostic approach of suspected pulmonary embolism (PE). However, the possibility of improving the conventional prediction rule for PE by integrating ultrasound has never been investigated., Methods: We performed lung and venous ultrasound in consecutive patients suspected of PE in four emergency departments. Conventional Wells score (Ws) was adjudicated by the attending physician, and ultrasound was performed by one of 20 investigators. Signs of deep venous thrombosis (DVT) at venous ultrasound and signs of pulmonary infarcts or alternative diagnoses at lung ultrasound were considered to recalculate two items of the Ws: signs and symptoms of DVT and alternative diagnosis less likely than PE. The diagnostic performances of the ultrasound-enhanced Ws (USWs) and Ws were then compared after confirmation of the final diagnosis., Results: A total of 446 patients were studied. PE was confirmed in 125 patients (28%). USWs performed significantly better than Ws, with a sensitivity of 69.6% versus 57.6% and a specificity of 88.2% versus 68.2%. In combination with D-dimer, USWs showed an optimal failure rate (0.8%) and a significantly superior efficiency than Ws (32.3% vs. 27.2%). A strategy based on lung and venous ultrasound combined with D-dimer would allow to avoid CT pulmonary angiography in 50.5% of patients with suspected PE, compared to 27.2% when the rule without ultrasound is applied., Conclusions: A pretest risk stratification enhanced by ultrasound of lung and venous performs better than Ws in the early diagnostic process of PE., (© 2016 by the Society for Academic Emergency Medicine.)

The decision to discharge in patients affected by acute exacerbation of COPD remains a common problem due to the complexity of the assessment of clinical recovery, with early readmission perceived as a marker of incompleteness of the received treatment. The neural respiratory drive, assessed by parasternal muscle electromyography, represents an estimate of the load imposed to the respiratory muscles and it may identify early clinical deterioration. The test is noninvasive, may be executed bedside, but requires experienced operators. Yet, feasibility and clinical interpretation outside reference centers seem to be the main unsolved issues in the implementation of the technique in clinical practice.

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by a high disability and increasing mortality. Bronchodilators are the cornerstone of pharmacological treatment in COPD, while therapeutic optimization with an improvement in symptoms and compliance represent the actual goals. This has led to the development of devices that combine different classes of inhalatory drugs. Recently, a novel combination of the long acting antimuscarinic agent glycopyrronium bromide and the beta2-agonist formoterol fumarate has been developed in a metered dose inhaler delivery system., Areas Covered: The present article will discuss the current unmet needs in pharmacological therapy of COPD, will then briefly cover the pharmacokinetic and pharmacodynamic characteristics of the formoterol/glycopyrronium fixed dose combination and present the novel delivery system based on engineered microparticles and the co-suspension technology. Finally, efficacy and safety results of phase I, II and III trials will be reviewed. Expert commentary: The novel combination therapy of formoterol/glycopyrronium is the first available as a metered dose inhaler and proved to have a good efficacy and safety profile compared to monocomponents and tiotropium. Although still limited, data from phase III trials provide good evidence to consider it a valid option in the pharmacological management of patients with COPD.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. Clinical features of the disease include exertional dyspnea and chronic cough, while persistent airflow obstruction detected at spirometry is the defining element of the disease. Notably, subjects with smoke exposure and symptoms, but normal FEV1/FVC ratio (previously classified as "stage 0" by the GOLD classification), are not considered affected and do not require treatment according to guidelines. The recent GeneCOPD study suggested that a proportion of this population might present significant radiological features of respiratory disease. This commentary article focuses on the possible future role of chest imaging, including ultrasound of the respiratory muscles, integrated with additional functional tests, such as body plethysmography and diffusing capacity for carbon monoxide of the lungs (DLCO), in a multidimensional assessment of COPD.

Ultrasonography is the only non-invasive, non-ionizing imaging technique widely available to directly assess diaphragmatic function. Two different sonographic approaches permit the assessment of muscle thickening in the zone of apposition and excursion of the dome of the diaphragm. Thanks to the new hand-held ultrasound instruments, the morphology and function of the diaphragm can be assessed in different settings, such as outpatient clinic, pulmonary function test laboratory, hospital department and intensive care unit, and under different conditions. Despite the existence of different acoustic views and several codified approaches, a comprehensive sonographic examination has never been standardized for clinical use. In this review, we summarize the clinical indications, methods and perspectives of the technique in adults., (© 2016 S. Karger AG, Basel.)

Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.

Breathlessness is a key symptom in chronic obstructive pulmonary disease (COPD) with prognostic implications on health status and survival. Since most conditions underlying chronic refractory breathlessness in COPD are not modifiable, the use of opioids and benzodiazepines has been proposed to relieve it. However, respiratory depression is a known adverse event of these drugs, and concerns have been raised on their use in patients with chronic respiratory failure. Despite safety-related concerns, benzodiazepines are frequently prescribed for a variety of reasons, including treatment of insomnia, depression and anxiety, as well as to relieve refractory dyspnea in patients with COPD. The key role of opioids in the end-of-life and in the management of dyspnea that is unresponsive to best-possible disease management is recognized. Moreover, the use of low dose opioids to treat dyspnea, discomfort or refusal for patient undergoing non-invasive ventilation is still debated. In the current review, we aim at discussing and analyzing recently published findings on the use of benzodiazepines and opioids in patients with COPD and at reviewing the literature on this topic. Recent observations favor the use of lower doses of opioids (≤30 mg oral morphine equivalents/day) for reduction of symptoms in those patients with severe COPD receiving long-term oxygen therapy. Low dose opioids are not associated with an increased risk of hospital admission or death in cohorts of COPD patients on long term oxygen therapy. On the contrary, benzodiazepines and opioids at higher doses might increase mortality.

Bronchial asthma is a chronic disease characterized by airway hyperresponsiveness, airway inflammation and remodelling. The hypothesis that the illness is inflammatory in nature has recently been challenged by studies showing that airway smooth muscle (ASM) plays a more important role than previously thought. For example, it is now known that in asthma patients, ASM proliferates more and faster than in healthy subjects, carries intrinsic defects and exhibits impaired relaxation, increased velocity of shortening, plastic adaptation to short length and perturbed equilibrium of actin-to-myosin during cycling. Similar conclusions can be drawn from studies on airway mechanics. For instance, in asthma, abnormal ASM contributes to limiting the response to deep lung stretching and accelerates the return of bronchial tone to baseline conditions, and contributes to increased airway stiffness. Upon stimulation, ASM causes airway narrowing that is heterogeneous across the lung and variable over time. This heterogeneity leads to patchy ventilation. Experimental studies have shown that patchy ventilation may precipitate an asthma attack, and inability to maintain bronchial tone control over time can predict the occurrence of bronchospastic attacks over a matter of a few days. To improve our knowledge on the pathogenesis of asthma, we believe that it is necessary to explore the disease within the framework of the topographical, volume and time domains of the lung that play an important role in setting the severity and progression of the disease. Application of the forced oscillation technique and multiple breath nitrogen washout may, alone or in combination, help address questions unsolvable until now., (© 2014 Asian Pacific Society of Respirology.)

Background: Lung ultrasound is a non-radiating accurate alternative tool to chest X-ray (CXR) in the diagnosis of community-acquired pneumonia (CAP) in adults., Objectives: The aim of our study was to define the accuracy of ultrasound in the diagnosis of CAP in children., Methods: 107 consecutive children with suspected CAP underwent clinical examination, blood sample analysis, CXR and lung ultrasound on admission to the Pediatric Department of the San Paolo Hospital. The diagnosis of pneumonia was made by an independent committee of physicians on the basis of the overall clinical and CXR data., Results: The diagnosis of CAP was confirmed by the committee in 81 patients (76%). Ultrasound and CXR were performed in all patients. Ultrasound had a sensitivity of 94% and specificity of 96%, while CXR showed a sensitivity of 82% and a specificity of 94%. In patients with CAP, ultrasound revealed subpleural consolidations with air bronchogram in 70 cases and focal B-lines in 6. A parapneumonic pleural effusion was detected in 17 patients by ultrasound, while only 11 of them could be detected by CXR., Conclusions: In our series, lung ultrasound was highly accurate for the diagnosis of CAP in hospitalized children. These results provide the rationale for a multicenter study in children.

Purpose: Pressure preset ventilation (PPV) modes with set inspiratory time can be classified according to their ability to synchronize pressure delivery with patient's inspiratory efforts (i-synchronization). Non-i-synchronized (like airway pressure release ventilation, APRV), partially i-synchronized (like biphasic airway pressure), and fully i-synchronized modes (like assist-pressure control) can be distinguished. Under identical ventilatory settings across PPV modes, the degree of i-synchronization may affect tidal volume (VT), transpulmonary pressure (PTP), and their variability. We performed bench and clinical studies., Methods: In the bench study, all the PPV modes of five ventilators were tested with an active lung simulator. Spontaneous efforts of -10 cmH2O at rates of 20 and 30 breaths/min were simulated. Ventilator settings were high pressure 30 cmH2O, positive end-expiratory pressure (PEEP) 15 cmH2O, frequency 15 breaths/min, and inspiratory to expiratory ratios (I:E) 1:3 and 3:1. In the clinical studies, data from eight intubated patients suffering from acute respiratory distress syndrome (ARDS) and ventilated with APRV were compared to the bench tests. In four additional ARDS patients, each of the PPV modes was compared., Results: As the degree of i-synchronization among the different PPV modes increased, mean VT and PTP swings markedly increased while breathing variability decreased. This was consistent with clinical comparison in four ARDS patients. Observational results in eight ARDS patients show low VT and a high variability with APRV., Conclusion: Despite identical ventilator settings, the different PPV modes lead to substantial differences in VT, PTP, and breathing variability in the presence spontaneous efforts. Clinicians should be aware of the possible harmful effects of i-synchronization especially when high VT is undesirable.

Purpose: To describe the practice, knowledge and beliefs about aerosol therapy during mechanical ventilation in an international sample of physicians working in intensive care units (ICU)., Methods: A self-administered survey was emailed to physicians who worked regularly in ICUs. The physicians were identified from the databases of the European and French societies of intensive care medicine and the REVA network., Results: Of the 1,192 responses (15 % response rate), 854 were analyzed. Of the respondents, who represented 611 departments in 70 countries, 99 % reported using aerosol therapy during mechanical ventilation (including non-invasive), 43 % exclusively used nebulizers and 55 % also used metered dose inhalers. Nebulization relied on jet, ultrasonic and vibrating mesh nebulizers (55 %, 44 % and 14 % of respondents, respectively). Bronchodilators and steroids were the most frequently delivered drugs, and 80 % of respondents had a positive opinion concerning nebulized colistin and 30 % reported the use of nebulized antibiotics at least every other month. During nebulization, ventilator settings were never changed by 77 % of respondents, 65 % reported placing a filter on the expiratory limb, and of these 28 % never changed it. Only 22 % of respondents using heated humidifiers reported turning them off during nebulization. Specific knowledge about droplet size and nebulization yield was poor. A majority of respondents (87 %) thought that ultrasonic nebulizers outperform jet nebulizers, while 69 % had no opinion concerning mesh nebulizers., Conclusions: Aerosol therapy during mechanical ventilation is used by over 95 % of intensivists, mostly for bronchodilator and steroid administration, but also frequently for antibiotics. The current scientific knowledge about optimal implementation seemed infrequently applied, suggesting the need for educational programs and research focusing on a better bench-to-bedside transfer of knowledge.

Background: Few prospective studies have evaluated the role of endobronchial needle aspiration in diagnosing central airways neoplasms. Rapid on-site evaluation has long been used in transbronchial needle aspiration of adenopathies and peripheral lesions, but its role in sampling central malignancies has not been substantiated yet., Objectives: In this study we evaluated if endobronchial needle aspiration may increase the sensitivity of bronchoscopy for diagnosing central airways neoplasms when added to conventional diagnostic methods (forceps biopsy, brushing and bronchial washing), and if rapid on-site evaluation may be beneficial in patients undergoing endobronchial needle aspiration., Methods: 125 patients (77% males, aged 70 ± 7 years; mean ± SD) with central lung cancers were randomized to undergo bronchoscopy including conventional diagnostic methods and needle aspiration, with or without rapid on-site evaluation, stratifying the patients on the basis of the neoplasm growth pattern (exophytic and submucosal/peribronchial disease)., Results: Needle aspiration significantly increased the sensitivity of bronchoscopy when added to conventional methods (from 76 to 91%; p < 0.001), primarily resulting from differences in submucosal/peribronchial diseases (68 vs. 90%; p < 0.001) and independently from the presence of rapid on-site evaluation; needle aspiration guided by rapid on-site evaluation guaranteed a higher improvement in bronchoscopy sensitivity than conventional needle aspiration (98 vs. 84%, respectively; p = 0.004). Needle aspiration guided by rapid on-site evaluation showed a significantly higher sensitivity than the conventional method (97 vs. 76%, respectively; p = 0.001)., Conclusions: Needle aspiration increases the sensitivity of bronchoscopy in diagnosing central airways malignancies when added to conventional diagnostic methods, with a further significant improvement when guided by rapid on-site evaluation., (Copyright © 2013 S. Karger AG, Basel.)

The interface is the defining element of non-invasive ventilation (NIV). Nowadays different types of interfaces, which differ in terms of shape, mechanical properties and comfort, are available, and their choice and fitting is a key element of NIV success. In the last decade, larger masks covering the entire face and specifically designed helmets have been developed for delivering NIV, theoretically improving comfort and patient tolerance. Recent studies have shown that, despite marked heterogeneity in mask internal volume and compliance, the dynamic dead space and, above all, the clinical efficacy of different masks is on average very similar. Thus, with the exception of the nasal mask and the mouthpiece, a variety of interfaces for NIV can be used in the acute care setting. However, prevention and monitoring of interfaces related side-effects and evaluation of patient tolerance are crucial to avoid NIV failure. To optimize effectiveness and costs, an interface strategy for NIV in acute respiratory failure could be convenient in clinical practice.

Purpose: Providing mechanical ventilation is challenging at supra-atmospheric pressure. The higher gas density increases resistance, reducing the flow delivered by the ventilator. A new hyperbaric ventilator (Siaretron IPER 1000) is said to compensate for these effects automatically. The aim of this bench test study was to validate the compensation, define its limits and provide details on the ventilator's output at varied atmospheric pressures., Methods: Experiments were conducted inside a multiplace hyperbaric chamber at 1, 2.2, 2.8 and 4 atmospheres absolute (ATA), with the ventilator connected to a test lung. Transducers were recalibrated at each ATA level. Various ventilator settings were tested in volume and pressure control modes. Measured tidal volumes were compared with theoretical predictions based on gas laws., Results: Results confirmed the ventilator's ability to provide compensation, but also identified its limits. The compensation range could be predicted and depended on the maximal flow attainable, decreasing linearly with increasing atmospheric pressure. With settings inside the range, tidal volumes approximated set values (mean error 10 ± 5 %). With settings outside the range, the volume was limited to the predicted maximal value calculated from maximal flow. A practical guide for clinicians is provided., Conclusion: The IPER 1000 ventilator attempted to deliver stable tidal volume by adjusting the opening of the inspiratory valve in proportion to atmospheric pressure. Adequate compensation was observed, albeit only within a predictable range, which can be reliably predicted for each setting and ATA level combination. Setting a tidal volume outside this range can result in an unwanted decrease in minute ventilation.

Unlabelled: The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion., Results: In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung., Conclusions: Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)