High-Flow Nasal Cannula and COVID-19: A Clinical Review.

During the coronavirus disease 2019 (COVID-19) pandemic, noninvasive respiratory support has played a central role in managing patients affected by moderate-to-severe acute hypoxemic respiratory failure, despite inadequate scientific evidence to support its usage. High-flow nasal cannula (HFNC) treatment has gained popularity because of its effectiveness in delivering a high fraction of humidified oxygen, which improves ventilatory efficiency and the respiratory pattern, as well as its reported high tolerability, ease of use, and application outside of ICUs. Nevertheless, the risk of infection transmission to health-care workers has raised some concerns about its use in the first wave of the pandemic outbreak, with controversial recommendations provided by different scientific societies. This narrative review provides an overview of the recent evidence on the physiologic rationale, risks, and benefits of using HFNC instead of conventional oxygen therapy and other types of noninvasive respiratory support devices, such as continuous positive airway pressure and noninvasive ventilation in patients affected by COVID-19 pneumonia with associated acute hypoxemic respiratory failure. It also summarizes the available evidence with regard to the clinical use of HFNC during the current pandemic and its reported outcomes, and highlights the risks of bioaerosol dispersion associated with HFNC use.

ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure.

BACKGROUND: High-flow nasal cannula (HFNC) has become a frequently used noninvasive form of respiratory support in acute settings; however, evidence supporting its use has only recently emerged. These guidelines provide evidence-based recommendations for the use of HFNC alongside other noninvasive forms of respiratory support in adults with acute respiratory failure (ARF). MATERIALS AND METHODOLOGY: The European Respiratory Society task force panel included expert clinicians and methodologists in pulmonology and intensive care medicine. The task force used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methods to summarise evidence and develop clinical recommendations for the use of HFNC alongside conventional oxygen therapy (COT) and noninvasive ventilation (NIV) for the management of adults in acute settings with ARF. RESULTS: The task force developed eight conditional recommendations, suggesting the use of 1) HFNC over COT in hypoxaemic ARF; 2) HFNC over NIV in hypoxaemic ARF; 3) HFNC over COT during breaks from NIV; 4) either HFNC or COT in post-operative patients at low risk of pulmonary complications; 5) either HFNC or NIV in post-operative patients at high risk of pulmonary complications; 6) HFNC over COT in nonsurgical patients at low risk of extubation failure; 7) NIV over HFNC for patients at high risk of extubation failure unless there are relative or absolute contraindications to NIV; and 8) trialling NIV prior to use of HFNC in patients with COPD and hypercapnic ARF. CONCLUSIONS: HFNC is a valuable intervention in adults with ARF. These conditional recommendations can assist clinicians in choosing the most appropriate form of noninvasive respiratory support to provide to patients in different acute settings.

Bronchoscopy during COVID-19 pandemic, ventilatory strategies and procedure measures.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has changed bronchoscopy practices worldwide. Bronchoscopy is a high-risk aerosol-generating procedure with a potential for direct SARS-CoV-2 exposure and hospital-acquired infection. Current guidelines about personal protective equipment and environment considerations represent key competencies to minimize droplets dispersion and reduce the risk of transmission. Different measures should be put in field based on setting, patient's clinical characteristics, urgency and indications of bronchoscopy. The use of this technique in SARS-CoV-2 patients is reported primarily for removal of airway plugs and for obtaining microbiological culture samples. In mechanically ventilated patients with SARS-CoV-2, bronchoscopy is commonly used to manage complications such as hemoptysis, atelectasis or lung collapse when prone positioning, physiotherapy or recruitment maneuvers have failed. Further indications are represented by assistance during percutaneous tracheostomy. Continuous positive airway pressure, non-invasive ventilation support and high flow nasal cannula oxygen are frequently used in patient affected by Coronavirus disease 2019 (COVID-19): management of patients' airways and ventilation strategies differs from bronchoscopy indications, patient's clinical status and in course or required ventilatory support. Sedation is usually administered by the pulmonologist (performing the bronchoscopy) or by the anesthetist depending on the complexity of the procedure and the level of sedation required. Lastly, elective bronchoscopy for diagnostic indications during COVID-19 pandemic should be carried on respecting rigid standards which allow to minimize potential viral transmission, independently from patient's COVID-19 status. This narrative review aims to evaluate the indications, procedural measures and ventilatory strategies of bronchoscopy performed in different settings during COVID-19 pandemic.

Adult Pulmonary Intensive and Intermediate Care Units: The Italian Thoracic Society (ITS-AIPO) Position Paper.

The imbalance between the prevalence of patients with acute respiratory failure (ARF) and acute-on-chronic respiratory failure and the number of intensive care unit (ICU) beds requires new solutions. The increasing use of non-invasive respiratory tools to support patients at earlier stages of ARF and the increased expertise of non-ICU clinicians in other types of supportive care have led to the development of adult pulmonary intensive care units (PICUs) and pulmonary intermediate care units (PIMCUs). As in other European countries, Italian PICUs and PIMCUs provide an intermediate level of care as the setting designed for managing ARF patients without severe non-pulmonary dysfunction. The PICUs and PIMCUs may also act as step-down units for weaning patients from prolonged mechanical ventilation and for discharging patients still requiring ventilatory support at home. These units may play an important role in the on-going coronavirus disease 2019 pandemic. This position paper promoted by the Italian Thoracic Society (ITS-AIPO) describes the models, facilities, staff, equipment, and operating methods of PICUs and PIMCUs.

The lung microbiome: clinical and therapeutic implications.

The human respiratory tract, usually considered sterile, is currently being investigated for human-associated microbial communities. According to Dickson's conceptual model, the lung microbiota (LMt) is a dynamic ecosystem, whose composition, in healthy lungs, is likely to reflect microbial migration, reproduction, and elimination. However, which microbial genera constitutes a "healthy microbiome" per se remains hotly debated. It is now widely accepted that a bi-directional gut-lung axis connects the intestinal with the pulmonary microbiota and that the diet could have a role in modulating both microbiotas as in health as in pathological status. The LMt is altered in numerous respiratory disorders such as obstructive airway diseases, interstitial lung diseases, infections, and lung cancer. Some authors hypothesize that the use of specific bacterial strains, termed "probiotics," with positive effects on the host immunity and/or against pathogens, could have beneficial effects in the treatment of intestinal disorders and pulmonary diseases. In this manuscript, we have reviewed the literature available on the LMt to delineate and discuss the potential relationship between composition alterations of LMt and lung diseases. Finally, we have reported some meaningful clinical studies that used integrated probiotics' treatments to contrast some lung-correlated disorders.

Competences in bronchoscopy for Intensive Care Unit, anesthesiology, thoracic surgery and lung transplantation.

Over the last decades, the use of flexible bronchoscopy has greatly increased in intensive care, anesthesia and thoracic surgery for diagnostic purpose, management of critical patients and to facilitate airway management for tracheal intubation, one lung ventilation and lung transplant management. The huge availability of endoscopic instruments and devices for airway management has amplified indications and possibilities for bronchoscopic procedures performed by intensive care physicians, anesthesiologist, endoscopists, and surgeons too. These practices need adequate technical skills that can be acquired only through defined learning pathways. This manuscript summarizes the indications and the competencies needed to perform bronchoscopic procedures in intensive care, anesthesia and thoracic surgery settings.

Assessment of asthma control: the SERENA study.

BACKGROUND: Several studies suggest that many asthmatic subjects have uncontrolled asthma. The control of asthma is now considered the major goal of therapy. OBJECTIVES: to ascertain the level of asthma control, by Asthma Control Test (ACT), in "real-life" clinical practice and the potential risk factors for uncontrolled disease in patients treated with inhaled corticosteroids (ICS) and long-acting beta-adrenergic agonists (LABA). METHODS: SERENA is a multi-centre, cross-sectional, 6-month observational, non-interventional study carried out in 16 Pulmonary Units in Italy. Asthmatic outpatients aged over 18, undergoing treatment with ICS at medium-high daily doses associated with LABA, were enrolled. The patients were divided in 3 subgroups according to the level of asthma control by ACT score (25:controlled; 20-24:partly controlled; <20: uncontrolled). RESULTS: Out of a total of 548 patients, 396 met the inclusion criteria. Only 9.1% of patients had asthma controlled, while partly controlled and uncontrolled asthma accounted for 39.6% and 51.3% respectively. The mean age was 54.5 ± 15.8 and the mean duration of asthma was 16.1 ± 14.1 years. There were more females than males (63% vs 37%) and females had highest prevalence of uncontrolled asthma (63.1%). The mean values of FEV1% predicted were lower in the uncontrolled group (p < 0.001). The percentage of patients with at least 1 exacerbation, unscheduled visit and/or admissions was lower in controlled (22.2%, 8.3%, 8.3%) than in partly controlled (50%, 38.6%, 9.2%) and uncontrolled (83.2%, 66.2%, 27.8%) groups (p < 0.0001). The multivariate ordinal logistic regression analysis identified female sex, FEV1 and exacerbations as the strongest independent factors associated with the uncontrolled disease. CONCLUSION: This study highlights the importance in clinical practice of a periodic assessment by a validated asthma control instrument and exacerbations/health care contacts during previous year. Clinicians should be aware that a significant proportion of patients can have uncontrolled asthma, despite regular pharmacological treatment.

Update on optimal use of omalizumab in management of asthma.

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.

Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma.

Airway smooth muscle (ASM) plays a key role in bronchomotor tone, as well as in structural remodeling of the bronchial wall. Therefore, ASM contraction and proliferation significantly participate in the development and progression of asthma. Many contractile agonists also behave as mitogenic stimuli, thus contributing to frame a hyperresponsive and hyperplastic ASM phenotype. In this review, the molecular mechanisms and signaling pathways involved in excitation-contraction coupling and ASM cell growth will be outlined. Indeed, the recent advances in understanding the basic aspects of ASM biology are disclosing important cellular targets, currently explored for the implementation of new, more effective anti-asthma therapies.

Omalizumab in the treatment of severe asthma: efficacy and current problems.

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing their interactions with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high-affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include relevant improvements in respiratory symptoms and quality of life, paralleled by a marked reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma, inadequately controlled by high doses of standard inhaled treatments.

Effects of TGF-beta and glucocorticoids on map kinase phosphorylation, IL-6/IL-11 secretion and cell proliferation in primary cultures of human lung fibroblasts.

Transforming growth factor-beta1 (TGF-beta1) is crucially involved in the fibrotic events characterizing interstitial lung diseases (ILDs), as well as in the airway remodeling process typical of asthma. Within such a context, the aim of our study was to investigate, in primary cultures of normal and fibrotic human lung fibroblasts (HLFs), the effects of TGF-beta1 on mitogen-activated protein kinase (MAPK) phosphorylation, cell proliferation, and production of interleukins 6 (IL-6) and 11 (IL-11), in the presence or absence of a pretreatment with budesonide (BUD). MAPK phosphorylation was detected by Western blotting, cell viability and proliferation were evaluated using Trypan blue staining and [(3)H]-thymidine incorporation assay, respectively, and the release of IL-6 and IL-11 into cell culture supernatants was assessed by ELISA. TGF-beta1 (10 ng/ml) significantly stimulated MAPK phosphorylation (P < 0.01), and also enhanced cell proliferation as well as the secretion of both IL-6 and IL-11, which reached the highest increases at the 72nd h of cell exposure to this growth factor. All such effects were prevented by BUD (10(-8) M) and, with the exception of IL-6 release, also by a mixture of MAPK inhibitors. Therefore, our findings suggest that the fibrotic action exerted by TGF-beta1 in the lung is mediated at least in part by MAPK activation and by an increased synthesis of the profibrogenic cytokines IL-6 and IL-11; all these effects appear to be prevented by corticosteroids via inhibition of MAPK phosphorylation.

Respiratory infections and asthma.

Respiratory tract infections caused by both viruses and/or atypical bacteria are involved in the pathogenesis of asthma. In particular, several viruses such as respiratory syncytial virus, rhinovirus and influenza/parainfluenza viruses may favour the expression of the asthmatic phenotype, being also implicated in the induction of disease exacerbations. Within this pathological context, a significant role can also be played by airway bacterial colonizations and infections due to Chlamydiae and Mycoplasms. All these microbial agents probably interfere with complex immunological pathways, thus contributing to induce and exacerbate asthma in genetically predisposed individuals.

Biological targets for therapeutic interventions in COPD: clinical potential.

COPD is a widespread inflammatory respiratory disorder characterized by a progressive, poorly reversible airflow limitation. Currently available therapies are mostly based on those used to treat asthma. However, such compounds are not able to effectively reduce the gradual functional deterioration, as well as the ongoing airway and lung inflammation occurring in COPD patients. Therefore, there is an urgent need to improve the efficacy of the existing drug classes and to develop new treatments, targeting the main cellular and molecular mechanisms underlying disease pathogenesis. These therapeutic strategies will be highlighted in the present review.