Feasibility and clinical impact of a portable bi-level ventilation device in patients with severe chronic obstructive pulmonary disease and exertional dyspnea: preliminary results from a clinical series.

We explore home use of a portable bi-level ventilation device among patients with severe chronic obstructive pulmonary disease (COPD), and describe changes in the patients' physical activity levels, perceived dyspnea, anxiety and depression, as well as their satisfaction with the device, after one month of use. METHODS: Forty patients with severe COPD and exertional dyspnea were instructed to use VitaBreath® device (Philips, Respironics) during efforts or activities of daily living for 4 weeks, and agreed to answer questionnaires on anxiety, depression, dyspnea and physical activity. RESULTS: Twenty-six (65%) patients used the VitaBreath® device for four weeks, while 14 patients (35%) stopped early for various reasons. Among patients who completed the 4-week course, no differences in dyspnea and physical activity were observed between baseline and follow-up (p-values 0.41 and 0.19, respectively). Thirteen (50%) and 15 (57%) patients experienced reduced anxiety and depression, respectively. Patients with greater functional impairment and less autonomy in activities of daily living tended to view the device more positively. CONCLUSION: Home use of portable bi-level positive-pressure ventilation devices by patients with COPD may alleviate disease-related anxiety and depression, particularly in more severe cases of COPD. Future portable device design should feature adjustable inspiratory/expiratory pressures.

Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study.

BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18-75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO2]/fractional concentration of oxygen in inspired air [FiO2]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m2 (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO2/FiO2 ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9-65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO2/FiO2 ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 103/µL [101·9] vs 319·8 × 103/µL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.

Management of Chronic Respiratory Failure in Interstitial Lung Diseases: Overview and Clinical Insights.

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.

Noninvasive Ventilation Weaning in Acute Hypercapnic Respiratory Failure due to COPD Exacerbation: A Real-Life Observational Study.

The most recent British Thoracic Society/Intensive Care Society (BTS/ICS) guidelines on the use of noninvasive ventilation (NIV) in acute hypercapnic respiratory failure (AHRF) suggest to maximize NIV use in the first 24 hours and to perform a slow tapering. However, a limited number of studies evaluated the phase of NIV weaning. The aim of this study is to describe the NIV weaning protocol used in AHRF due to acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), patients' characteristics, clinical course, and outcomes in a real-life intermediate respiratory care unit (IRCU) setting. We performed a retrospective study on adult patients hospitalized at the IRCU of San Gerardo Hospital, Monza, Italy, from January 2015 to April 2017 with a diagnosis of AHRF due to COPD exacerbation. The NIV weaning protocol used in our institution consists of the interruption of one of the three daily NIV sessions at the time, starting from the morning session and finishing with the night session. The 51 patients who started weaning were divided into three groups: 20 (39%) patients (median age 80 yrs, 65% males) who completed the protocol and were discharged home without NIV (Completed Group), 20 (39%) did not complete it because they were adapted to domiciliary ventilation (Chronic NIV Group), and 11 (22%) interrupted weaning ex abrupto mainly due to NIV intolerance (Failed Group). Completed Group patients were older, had a higher burden of comorbidities, but a lower severity of COPD compared to Chronic NIV Group. Failed Group patients experienced higher frequency of delirium after NIV discontinuation. None of the patients who completed weaning had AHRF relapse during hospitalization. While other NIV weaning methods have been previously described, our study is the first to describe a protocol that implies the interruption of a ventilation session at the time. The application of a weaning protocol may prevent AHRF relapse in the early stages of NIV interruption and in elderly frail patients.

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.

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.

Positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: do we need a personalized approach?

BACKGROUND: Acute respiratory failure (ARF) is a life-threatening complication in patients with community acquired pneumonia (CAP). The use of non-invasive ventilation is controversial. With this prospective, observational study we aimed to describe a protocol to assess whether a patient with moderate-to-severe hypoxemic ARF secondary to CAP benefits, in clinical and laboratoristic terms, from the application of a positive end expiratory pressure (PEEP) + oxygen vs oxygen alone. METHODS: Patients who benefit from PEEP application (PEEP-responders) were defined as those with partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increase >20% and/or reduction of respiratory distress during PEEP + oxygen therapy compared to oxygen therapy alone. Clinical characteristics and outcomes were compared between PEEP-responders and PEEP-non responders. RESULTS: Out of 41 patients, 27 (66%) benefit from PEEP application (PEEP-responders), the best response was obtained with a PEEP of 10 cmH2O in 13 patients, 7.5 cmH2O in eight and 5 cmH2O in six. PEEP-responders were less likely to present comorbidities compared to PEEP-non responders. No differences between groups were found in regards to endotracheal intubation criteria fullfillment, intensive care unit admission and in-hospital mortality, while PEEP-responders had a shorter length of hospital stay. DISCUSSION: The application of a protocol to evaluate PEEP responsiveness might be useful in patients with moderate-to-severe hypoxemic ARF due to CAP in order to personalize and maximize the effectiveness of therapy, and prevent the inappropriate PEEP use. PEEP responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay.

Corticosteroid and cyclophosphamide in acute exacerbation of idiopathic pulmonary fibrosis: a single center experience and literature review.

Acute Exacerbation (AEx) is a frequent and severe complication of Idiopathic Pulmonary Fibrosis (IPF). In the absence of consensus regarding treatment, studies evaluating the efficacy of specific therapies, such as corticosteroids and immunosuppresant agents, are needed. In this case series we evaluated the outcome in terms of survival of intravenous pulse doses of high-dose corticosteroid (methylprednisolone 1000 mg per day for 3 consecutive days) followed by montlhy cyclophosphamide administration (maximum 6 doses) in a cohort of patients with AEx-IPF referred to the Respiratory Unit, San Gerardo University Hospital, Monza, Italy, from 2009 to 2013. A total of 11 patients (7 males, median age 65 years) were enrolled. A median of five monthly pulse doses of cyclophosphamide were administered, with four patients receiving all 6 doses. Four patients died before completion. Three patients developed adverse events. Overall survival at 3 months was 73%, at 6 months 63%, at 12 months 55%, at 18 months 45% and at 2 years 27%. In-hospital mortality was 9%. Causes of death were: six respiratory failures from disease progression, one lung cancer and one breast cancer. Two patients received lung transplantation and were excluded from the Kaplan-Meier analysis. In conclusion, combined intravenous pulse doses of high-dose corticosteroid and cyclophosphamide could be a reasonable add-on therapy for AEx-IPF, considering the few side effects and safe profile. A complete and rapid diagnostic work-up associated to the proper management (e.g. support of respiratory failure with non-invasive ventilation) in the right setting, may also have a positive effect on patients' outcome.

Delirium symptoms during hospitalization predict long-term mortality in patients with severe pneumonia.

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.

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.

Non-invasive mechanical ventilation in patients with diffuse interstitial lung diseases.

BACKGROUND: 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. METHODS: In a multicenter, observational, retrospective study, consecutive DILD patients undergoing NIV because of an episode of ARF were evaluated in six Italian high dependency units. Three groups of patients were identified based on the etiology of ARF: those with pneumonia (Group A), those with acute exacerbation of fibrosis, (Group B) and those with other triggers (Group C). Clinical failure was defined as any among in-hospital mortality, endotracheal intubation and extra-corporeal membrane oxygenation use. RESULTS: Among the 60 patients enrolled (63% males; median age: 71 years), pneumonia (42%) and acute exacerbation of fibrosis (39%) were the two most frequent causes of ARF. A significant increase of PaO2/FiO2 ratio during NIV treatment was detected in Group A (p = 0.010), but not in Group B. No significant difference in PaO2/FiO2 ratio, PaCO2 and pH values during NIV treatment was detected in patients with a radiological pattern of usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). 22 patients (37%) suffered for a clinical failure. No significant differences in the study outcome were detected in Group A vs. Group B, as well as among patients with a radiological pattern of UIP vs. NSIP CONCLUSIONS: NIV treatment should be individualized in DILD patients with ARF according to the etiology, but not the baseline radiological pattern, in order to improve oxygenation.

Influenza A/H1N1 Severe Pneumonia: Novel Morphocytological Findings in Bronchoalveolar Lavage.

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.

Optimization of ventilator setting by flow and pressure waveforms analysis during noninvasive ventilation for acute exacerbations of COPD: a multicentric randomized controlled trial.

INTRODUCTION: The analysis of flow and pressure waveforms generated by ventilators can be useful in the optimization of patient-ventilator interactions, notably in chronic obstructive pulmonary disease (COPD) patients. To date, however, a real clinical benefit of this approach has not been proven. METHODS: The aim of the present randomized, multi-centric, controlled study was to compare optimized ventilation, driven by the analysis of flow and pressure waveforms, to standard ventilation (same physician, same initial ventilator setting, same time spent at the bedside while the ventilator screen was obscured with numerical data always available). The primary aim was the rate of pH normalization at two hours, while secondary aims were changes in PaCO2, respiratory rate and the patient's tolerance to ventilation (all parameters evaluated at baseline, 30, 120, 360 minutes and 24 hours after the beginning of ventilation). Seventy patients (35 for each group) with acute exacerbation of COPD were enrolled. RESULTS: Optimized ventilation led to a more rapid normalization of pH at two hours (51 vs. 26% of patients), to a significant improvement of the patient's tolerance to ventilation at two hours, and to a higher decrease of PaCO2 at two and six hours. Optimized ventilation induced physicians to use higher levels of external positive end-expiratory pressure, more sensitive inspiratory triggers and a faster speed of pressurization. CONCLUSIONS: The analysis of the waveforms generated by ventilators has a significant positive effect on physiological and patient-centered outcomes during acute exacerbation of COPD. The acquisition of specific skills in this field should be encouraged. TRIAL REGISTRATION: ClinicalTrials.gov NCT01291303.

Recurrent giant hemangioma causing severe respiratory distress.

Hemangioma is a common benign tumor of the liver that is usually asymptomatic. If >4 cm (giant hemangioma), it could present symptoms related to bleeding, thrombosis, consumptive coagulopathy, or adjacent abdominal organ compression. If symptomatic surgical treatment should be considered, liver resection as well as enucleation are considered. Recurrences after surgical resection are rare. We herein present a case of woman admitted to the emergency room for acute severe respiratory distress. She had undergone 2 surgical resections of liver hemangiomas. The respiratory syndrome, as showed by chest x-ray, computed tomography scan, and nuclear magnetic resonance imaging, was related to a recurrent giant multiple hemangioma, creating a prominent compression of right lung with left mediastinal shift and left heart dislocation. It resulted in pulmonary parenchymal compression associated with reduced chest wall compliance and increased pulmonary pressure. The patient was not eligible for surgical treatment because of the disease extension and her clinical conditions. She died 6 months later from respiratory insufficiency and hypercapnic coma.