Expert Review of Respiratory Medicine最新文献

Background: Obstructive sleep apnea (OSA) and hypertension are interrelated diseases linked to gut dysbiosis. This study aimed to investigate the effect of OSA on the gut microbiome in the context of hypertension and vice versa.

Research design and methods: Of 211 consecutively screened patients, 52 completed polysomnography study, medical history questionnaires, and fecal sample collection. 16S rRNA gene sequencing was performed on fecal samples, and diversity, richness, and microbial taxa were analyzed using bioinformatics.

Results: Alpha diversity showed slightly decreased diversity in OSA and hypertension groups without significant difference, and the hypoxia burden index (HBI) showed a weak positive correlation with Chao1 index (r = 0.342, p < 0.05) in OSA patients. Firmicutes-to-Bacteroidetes ratio was higher in patients with than without OSA. In hypertensive patients, those with OSA had higher Ruminococcus_1, Lachnoclostridium, Lachnospira, [Ruminococcus]_torques_group, and unidentified Lachnospiraceae levels than those without OSA. Conversely, in OSA patients, hypertensive patients had lower Faecalibacterium and Lachnospiraceae_NK4A136_group levels.

Conclusion: The present study suggests a possible compensatory mechanism for gut microbiome changes in sleep apnea pathophysiology. The positive correlation between HBI and alpha diversity, and increase in certain genera of Ruminococcaceae and Lachnospiraceae in OSA patients may represent an adaptive response to hypoxia.

Introduction: Quitting is the only proven method to attenuate the progression of chronic obstructive pulmonary disease (COPD). However, most COPD smokers do not seem to respond to smoking cessation interventions and may benefit by lessening the negative health effects of long-term cigarette smoke exposure by switching to non-combustible nicotine delivery alternatives, such as heated tobacco products (HTPs) and e-cigarettes (ECs).

Areas covered: Compared with conventional cigarettes, HTPs and ECs offer substantial reduction in exposure to toxic chemicals and have the potential to reduce harm from cigarette smoke when used as tobacco cigarette substitutes. In this review, we examine the available clinical studies and population surveys on the respiratory health effects of ECs and HTPs in COPD patients.

Expert opinion: The current research on the impact of ECs and HTPs on COPD patients' health is limited, and more high-quality studies are needed to draw definitive conclusions. However, this review provides a comprehensive overview of the available literature for health professionals looking to advise COPD patients on the use of these products. While ECs and HTPs may offer some benefits in reducing harm from cigarette smoke, their long-term effects on COPD patients' health are still unclear.

Introduction: The study of genetic variants in response to different drugs has predominated in fields of medicine such as oncology and infectious diseases. In chronic respiratory diseases, the available pharmacogenomic information is scarce but not less relevant.

Areas covered: We searched the pharmacogenomic recommendations for respiratory diseases in the Table of Pharmacogenomic Biomarkers in Drug Labeling (U.S. Food and Drug Administration), the Clinical Pharmacogenomics Implementation Consortium (CPIC), and PharmGKB. The main pharmacogenomics recommendation in this field is to assess CFTR variants for using ivacaftor and its combination. The drugs' labels for arformoterol, indacaterol, and umeclidinium indicate a lack of influence of genetic variants in the pharmacokinetics of these drugs. Further studies should evaluate the contribution of CYP2D6 and CYP2C19 variants for formoterol. In addition, there are reports of potential pharmacogenetic variants in the treatment with acetylcysteine (TOLLIP rs3750920) and captopril (ACE rs1799752). The genetic variations for warfarin also are presented in PharmGKB and CPIC for patients with pulmonary hypertension.

Expert opinion: The pharmacogenomics recommendations for lung diseases are limited. The clinical implementation of pharmacogenomics in treating respiratory diseases will contribute to the quality of life of patients with chronic respiratory diseases.

Background: Many patients need repeated bronchoscopies with tissue sampling to obtain the final pathological results and guide the optimal subsequent treatment of pulmonary lesions. However, few studies have explored the safety of repeated biopsies.

Methods: The records of patients who underwent bronchoscopy-guided tissue sampling because of pulmonary lesions at the respiratory department between 1 January 2008 and 31 December 2019 were revised. The patients' clinical characteristics, information about bronchoscopy and incidence of complications were collected and analyzed.

Results: In total, 3899 bronchoscopy-guided tissue sampling procedures were conducted in the 1781 participants. There was no significant difference in the incidence of major complications between the initial bronchoscopies and repeated bronchoscopies (1.12% vs. 1.13%, χ² < 0.01, df = 1, p = 0.98), as was the incidence of hemoptysis (χ² = 2.18, df = 1, p = 0.14). However, the bleeding rate of patients who experienced bleeding during the first bronchoscopies was significantly higher than that of patients who did not experience bleeding (61.19% vs. 32.63%, χ² = 253.00, df = 1, p < 0.01).

Conclusions: For patients with pulmonary lesions, re-bronchoscopy with tissue sampling appears to infer the same risk of bleeding including severe bleeding as experienced during the initial bronchoscopy. However, it should be treated with discretion when performing repeated tissue sampling on patients who once bled.

Introduction: Pneumocystis jirovecii is an opportunistic, human-specific fungus that causes Pneumocystis pneumonia (PCP). PCP symptoms are nonspecific. A patient with P. jirovecii and another lung infection faces a diagnostic challenge. It may be difficult to determine which of these agents is responsible for the clinical symptoms, preventing effective treatment. Diagnostic and treatment efforts have been made more difficult by the rising frequency with which coronavirus 2019 (COVID-19) and PCP co-occur.

Areas covered: Herein, we provide a comprehensive review of clinical and pharmacological recommendations along with a literature review of PCP in immunocompromised patients focusing on HIV-uninfected patients.

Expert opinion: PCP may be masked by identifying co-existing pathogens that are not necessarily responsible for the observed infection. Patients with severe form COVID-19 should be examined for underlying immunodeficiency, and co-infections must be considered as co-infection with P. jirovecii may worsen COVID-19's severity and fatality. PCP should be investigated in patients with PCP risk factors who come with pneumonia and suggestive radiographic symptoms but have not previously received PCP prophylaxis. PCP prophylaxis should be explored in individuals with various conditions that impair the immune system, depending on their PCP risk.

Introduction: Lung transplantation (LTx) remains the only therapeutic strategy for patients with incurable lung diseases. However, its use has been severely limited by the narrow donor pool and potential concerns of inferior quality of donor lungs, which are more susceptible to external influence than other transplant organs. Multiple insults, including various causes of death and a series of perimortem events, may act together on donor lungs and eventually culminate in primary graft dysfunction (PGD) after transplantation as well as other poor short-term outcomes.

Areas covered: This review focuses on the predisposing factors contributing to injuries to the donor lungs, specifically focusing on the pathogenesis of these injuries and their impact on post-transplant outcomes. Additionally, various maneuvers to mitigate donor lung injuries have been proposed.

Expert opinion: The selection criteria for eligible donors vary and may be poor discriminators of lung injury. Not all transplanted lungs are in ideal condition. With the rapidly increasing waiting list for LTx, the trend of using marginal donors has become more apparent, underscoring the need to gain a deeper understanding of donor lung injuries and discover more donor resources.

Introduction: Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice.

Areas covered: We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors.

Expert opinion: This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.

Introduction: Evidence from non-randomized studies shows benefits for single-inhaler users compared with multiple-inhaler users who receive the same medication. As a result, comparative cost-effectiveness studies are required to inform treatment decisions with an increasing choice of medications and devices for chronic obstructive pulmonary disease (COPD). This study conducted a systematic literature review to evaluate the cost-effectiveness of using a single combination inhaler regimen for patients with severe COPD. This review also investigated the health impact on patients in different settings.

Areas covered: A systematic literature search was conducted in PubMed (MEDLINE), EMBASE, Web of Science, Scopus, Cochrane Library, EBSCO Host (including CINAHL and EconLit), Health Technology Assessment Database, National Institute for Health Research Economic Evaluation Database, Cost-Effectiveness Analysis Registry and Google Scholar.

Expert opinion: Based on the primary findings of 13 included studies: (1) single-inhaler triple therapy was a cost-effective treatment option for patients with severe COPD, and (2) triple therapy also resulted in better health outcomes (reduced exacerbations, life-years gained) and increased QALYs for patients with severe COPD. Nonetheless, eleven out of the thirteen selected studies were funded by the pharmaceutical industry, and none were conducted in the least developed countries. Therefore, the results should be interpreted with caution.

Introduction: Pleural infection causes significant morbidity and mortality. An important aspect in the treatment of pleural infection is the pharmacokinetics of antibiotics, an area often neglected.

Areas covered: Pathophysiology of pleural infection and the importance of antibiotic therapy in the treatment of pleural infection are discussed. After reviewing all available literature on pharmacokinetics of antibiotics for pleural infection, the scarcity of data and knowledge gaps are highlighted.

Expert opinion: This review aims to heighten awareness of the limited pharmacokinetic data of commonly used antibiotics for pleural infection. It serves to remind clinicians that choice of antibiotics for pleural infection should be based not only on bacterial sensitivity but also adequate delivery of antibiotics to the infected pleural cavity. Antibiotic pharmacokinetics may vary with agents used, pleural thickness and individual characteristics. Consideration must be given to insufficient pleural delivery of systemic antibiotics in patients lacking clinical improvement. Pleural infection research has disproportionately focused on fluid drainage. Optimizing delivery of effective antibiotic therapy to the pleural cavity must be regarded a key priority to progress clinical care. Large comprehensive cohort studies on pharmacokinetic variability are the essential next step. The possibility of intrapleural administration is also an area that warrants additional research.

Background: Residual alveolar inflammation seems to be paramount in post-COVID pathophysiology. Currently, we still lack a reliable marker to detect and track alveolar phlogosis in these patients. Exhaled Breath Condensate (EBC) pH has robust evidences highlighting its correlation with lung phlogosis in various diseases. We aim to define the reliability of alveolar and bronchial EBC pH in the assessment and in the follow up of post-COVID-related inflammation.

Research design and methods: We enrolled 10 patients previously hospitalized due to COVID-19 pneumonia. We performed a complete follow-up after 3 months and 6 months from discharge. Each visit included routine blood tests, arterial blood gas analysis, 6-minute walking test, spirometry, diffusing capacity and body plethysmography. Finally, bronchial and alveolar EBC were collected at the end of each visit.

Results: Alveolar EBC pH was significantly lower than bronchial EBC pH at T1, alveolar EBC pH tended to be more acid after 3 months from hospital discharge compared to the same sample 6 months later. Serum inflammatory biomarkers showed no significant differences from T1 to T2. Alveolar EBC pH was positively correlated with neutrophil-lymphocyte ratio.

Conclusions: Collecting EBC pH could help to understand pathophysiologic mechanism as well as monitoring alveolar inflammation in the post-COVID syndrome.