Expert Review of Respiratory Medicine最新文献

Introduction: In recent years, monoclonal antibodies targeting Type-2 inflammatory pathways have been developed for severe asthma treatment. However, even when patients are carefully selected, the response to treatment varies.

Areas covered: Different studies have evaluated response to therapy with biologics such as exacerbation reduction, symptom improvement, pulmonary function increase, improvement in QoL, or decrease of oral corticosteroids, showing that all patients do not respond to all disease aspects and leading to an extensive debate regarding the definition of response.

Expert opinion: Assessing response to therapy is of great importance, but since there is no uniform definition of treatment response, the recognition of patients who really benefit from these therapies remains an unmet need. In the same context, identifying non-responding patients in which biologic therapy should be switched or substituted by alternative treatment options is of paramount importance. In this review, we present the road trip of the definition of therapeutic response to biologics in severe asthmatics by presenting the current relevant medical literature. We also present the suggested predictors of response, with an emphasis on the so-called super-responders. Finally, we discuss the recent insights regarding asthma remission as a feasible treatment goal and provide a simple algorithm for the evaluation of response.

Introduction: Stage III non-small cell lung cancer (NSCLC) is a composite of the regional spread of lung cancer with different levels of potential lymph node involvement and tumor size that often deem the stage at time of diagnosis to be unresectable and suitable for chemoradiation plus consolidation immunotherapy with durvalumab for 12 months. Chemoradiation plus durvalumab consolidation yielded a landmark 49.2% 5-year overall survival in unresectable NSCLC.

Areas covered: Sub-optimal results lead us to focus on the mechanisms of resistance responsible for intractability in a significant proportion of cases that fail with chemoradiation and immunotherapy. In stage III NSCLC it is opportune to explore the accumulated evidence on ferroptosis resistance that can lead to cancer progression and metastasis. Strong data shows that three anti-ferroptosis pathways are principally involved in resistance to chemotherapy, radiation, and immunotherapy.

Expert opinion: Because a large part of stage III NSCLCs is resistant to chemoradiation and durvalumab consolidation, a ferroptosis-based therapeutic approach, combined with standard-of-care therapy, can lead to improved clinical outcomes in patients diagnosed with stage III and possibly stage IV NSCLCs.

Introduction: Asthma comorbidities are a frequent cause of adverse outcomes, such as poor asthma control, frequent asthma attacks, reduced quality of life, and higher healthcare costs. Comorbidities are well-known treatable traits whose proper management can help achieve optimal asthma control. Although multimorbidity is frequent among asthmatics, comorbidities are still a potential cause of misdiagnosis and under or over treatments, and little is known about their impact on severe pediatric asthma.

Areas covered: We provided a comprehensive, 5-year updated review focusing on the main respiratory comorbidities in severe asthma, particularly in epidemiology, pathogenesis, and current and future therapies.

Expert opinion: Respiratory comorbidities have unique characteristics in childhood. Their management must be multidisciplinary, age-specific, and integrated. Further longitudinal studies are needed to understand better the mutual interrelation and synergistic effect between asthma and its respiratory comorbidities, the identification of common, treatable risk factors leading to potential asthma prevention, the effectiveness of actual and future target-therapies, and the correlation between long-lasting respiratory comorbidities and poor lung function trajectories.

Background: Interstitial lung disease (ILD) is a common complication of connective tissue diseases (CTD), but there are few clinical trials to guide disease management. We aimed to develop expert consensus statements and an algorithm for CTD-ILD management.

Research design and methods: Based on a targeted literature review, we developed 109 statements on managing CTD-ILD across six domains. We used a modified Delphi process to survey 22 physicians in Japan involved in managing CTD-ILD (specialists in pulmonology, rheumatology, pathology, and radiology). These panelists participated in two rounds of web-based survey to establish consensus statements, which were used to define an algorithm. Consensus was defined as a mean value ≥70 on a scale of 0 (strong disagreement) to 100 (strong agreement).

Results: Between May-August 2022, consensus was reached on 93 statements on CTD-ILD management. The most important consensus statements included screening CTD patients for ILD (typically with high-resolution computed tomography), using imaging, pulmonary function testing and serum biomarkers for diagnosis and severity assessment, regularly following up patients, and multidisciplinary management of CTD-ILD. Consensus statements were interpreted into an algorithm for clinical guidance.

Conclusions: Using the Delphi process, we have developed consensus statements and an algorithm to guide clinical decision-making for CTD-ILD.

Introduction: COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). As the respiratory tract is the primary site of infection and host-mediated inflammatory responses, pathologies and dysfunction of the respiratory system characterize the severe disease and are typically associated with the need for oxygen supply or even ventilator support. In survivors of severe COVID-19, computed tomography follow-up frequently reveals structural lung abnormalities, and one-third of individuals who were hospitalized during acute COVID-19 demonstrate persisting lung abnormalities for at least 12 months after disease onset.

Areas covered: This review summarizes current evidence on pulmonary recovery after COVID-19, focusing on adult patients who suffered from COVID-19 pneumonia.

Expert opinion: Severe COVID-19 is associated with a high frequency of persisting lung abnormalities at follow-up. The long-term consequences of these findings remain elusive and urge further evaluation to identify individuals at risk for COVID-19 long-term consequences.

Introduction: Asthma is commonly considered a disease of younger ages; however, it is not infrequent to pose a diagnosis of the disease in older individuals. Although current recommendations do not distinguish between young and old asthmatics in terms of diagnostic and therapeutic approaches, asthma in the elderly may present with peculiar features that contribute to complicate its management.

Areas covered: The current review focuses on the challenges that arise when approaching an older individual with suspected asthma. Age-associated changes of the lung may complicate the diagnostic approach. Measurement of the forced expiratory volume in the first 6 s (FEV6) in an easier and faster alternative to FVC estimation, and residual volume should always be assessed. Older individuals are often affected by concomitant diseases, both age- and drug-related, that need to be considered when approaching elderly asthmatics, since they can affect the efficacy of the treatment as well as the control of the disease.

Expert opinion: The potential drug to drug interaction should be routinely investigated, and documented in medical records. The effect of aging on the response to pharmacological therapy in older asthmatics should be explored. Therefore, the need of a multidisciplinary and multidimensional approach to the elderly asthmatics is strongly encouraged.

Background: Intermittent abdominal pressure ventilator (IAPV) use started in the 1930s for ventilatory assistance with muscular dystrophy patients. Later, the device was perfected and expanded for other neuromuscular disorders (NMD). In recent years, the morbidity and mortality tracheotomies and trach tubes related renewed the interest around IAPV. However, there are no guidelines for its use. This study aimed to establish a consensus among physicians involved in its practice to provide IAPV suggestions for the treatment of patients with NMD.

Method: A 3-step modified Delphi method was used to establish consensus. Fourteen respiratory physicians and one psychiatrist with strong experience in IAPV use and/or who published manuscripts on the topic participated in the panel. A systematic review of the literature was carried out according to the PRISMA to identify existing evidence on IAPV for patients with neuromuscular disorders.

Results: In the first round, 34 statements were circulated. Panel members marked 'agree' or 'disagree' for each statement and provided comments. The agreement was reached after the second voting session for all 34 statements.

Conclusions: Panel members agreed and IAPV indications, parameter settings (including procedure protocol), potential limitations, contraindications, complications, monitoring, and follow-up are described. This is the first expert consensus on IAPV.

Background: Currently, there are no universally accepted criteria to measure the response to biologics available as treatment for severe asthma. This survey aims to establish consensus criteria to use for the evaluation of response to biologics after 4 months of treatment.

Method: Using Delphi methodology, a questionnaire including 10 items was validated by 13 international experts in asthma. The electronic survey circulated within the Interasma Scientific Network platform. For each item, five answers were proposed graduated from 'no importance' to 'very high importance' and by a score (A = 2 points; B = 4 points; C = 6 points; D = 8 points; E = 10 points). The final criteria were selected if the median score for the item was ≥7 and > 60% of responses according 'high importance' and 'very high importance'. All selected criteria were validated by the experts.

Results: Four criteria were identified: reduce daily systemic corticosteroids dose by ≥50%; decrease the number of asthma exacerbations requiring systemic corticosteroids by ≥50%; have no/minimal side effects; and obtain asthma control according validated questionnaires. The consensual decision was that ≥3 criteria define a good response to biologics.

Conclusions: Specific criteria were defined by an international panel of experts and could be used as tool in clinical practice.

Introduction: Acute respiratory distress syndrome (ARDS) still represents a major challenge with high mortality rates and altered quality of life. Many well-designed studies have failed to improve ARDS outcomes. Heterogeneity of etiologies, mechanisms of lung damage, different lung mechanics, and different treatment approaches may explain these failures. At the era of personalized medicine, ARDS phenotyping is not only a field of research, but a bedside consideration when implementing therapy. ARDS has moved from being a simple syndrome to a more complex area of subgrouping. Intensivists must understand these phenotypes and therapies associated with a better outcome.

Areas covered: After a brief sum-up of the different type of ARDS phenotypes, we will present some relevant therapy that may be impacted by phenotyping. A focus on pharmacotherapy will be realized before a section on non-pharmaceutical strategies. Eventually, we will highlight the limits of our knowledge of phenotyping and the pitfalls of personalized medicine.

Expert opinion: Biological and morphological ARDS phenotypes are now well studied. The future of ARDS therapy will go through phenotyping that allows a personalized medication for each patient. However, a better assessment of these phenotypes is required, and clinical trials should be conducted with an ad-hoc phenotyping before randomization.