Current Opinion in Pulmonary Medicine最新文献

Purpose of review: Sleep disorders encompass a wide range of conditions with substantial individual variability. Epigenetics, the study of heritable changes beyond DNA sequence, offers a promising avenue for personalized medicine in this field.

Recent findings: There is great potential of epigenetic markers for sleep disorder diagnosis and the development of epigenetic drugs for targeted treatment. Epigenetic age acceleration, a marker of biological aging, is linked to sleep disorders and comorbidities. Very importantly, this acceleration may be reversible with effective treatment.

Summary: While the underlying mechanisms and assessment of clinical utility require further investigation, the potential of epigenetics in sleep medicine is recognized. Future research focused on closing knowledge gaps and clinical validation is crucial to translate these findings into practical applications, paving the way for more effective and personalized management of sleep disorders.

Purpose of review: In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor-tezacaftor-ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients.

Recent findings: Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI.

Summary: Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.

Purpose of review: Lung transplantation (LTX) has transformed care for people with cystic fibrosis (pwCF) suffering from advanced cystic fibrosis lung disease (ACFLD), and it has evolved into an accepted therapy for patients with ACFLD across all ages. We review cystic fibrosis as a major indication for LTX, particularly highlighting outcomes including survival, a changing landscape over time, and factors affecting sequelae following LTX in cystic fibrosis.

Recent findings: Although some populations such as those undergoing lung retransplantation exhibit inferior posttransplant outcomes, LTX for pwCF provides an excellent long-term survival that has significantly improved over time, likely due to specialized cystic fibrosis center care and recognition of common comorbidities in pwCF post-LTX. There are gaps in post-LTX outcomes for pwCF, including that identified between Canada and the United States, and that seen in adolescents - both of which are likely multifactorial. In particular, the revolution in cystic fibrosis medical therapy with CFTR modulator therapy has resulted in a dramatic decline in programs performing LTX for cystic fibrosis. How durable this effect will remains to be seen.

Summary: Overall, LTX remains a well accepted ultimate therapy option in patients with ACFLD if compatible with the individual's goals of care, offering an improved quality of life and maximization of overall survival.

Purpose of review: We aim to highlight two recent clinical trials that have altered the approach of the management of stage I nonsmall cell lung cancer.

Recent findings: The JCOG 0802 and CALGB 140503 trials demonstrated that sublobar resection is noninferior to lobectomy for overall and disease-free survival in patients with stage I nonsmall cell lung cancer.

Summary: Since 1962, lobectomy has been deemed the gold standard treatment for operable lung cancer. However, two recent clinical trials have demonstrated that, for select patients, sublobar resection is oncologically noninferior; results, which are leading us into a new era for the surgical management of lung cancer. Notwithstanding the progress made by these studies and the opportunities that have been put forth, questions remain. This review aims at reviewing the results of both trials and to discuss future perspectives for the surgical treatment of lung cancer.

Purpose of review: Lung transplantation activity continues to be limited by the availability of timely quality donor lungs. It is apparent though that progress has been made. The steady evolution of clinical practice, combined with painstaking scientific discovery and innovation are described.

Recent findings: There have been successful studies reporting innovations in the wider use and broader consideration of donation after circulatory death donor lungs, including an increasing number of transplants from each of the controlled, uncontrolled and medically assisted dying donor descriptive categories. Donors beyond age 70 years are providing better than expected long-term outcomes. Hepatitis C PCR positive donor lungs can be safely used if treated postoperatively with appropriate antivirals. Donor lung perfusion at a constant 10 degrees appears capable of significantly improving donor logistics and ex-vivo lung perfusion offers the potential of an ever-increasing number of novel donor management roles. Bioartificial and xenografts remain distant possibilities only at present.

Summary: Donor lungs have proved to be surprisingly robust and combined with clinical, scientific and engineering innovations, the realizable lung donor pool is proving to be larger than previously thought.

Purpose of review: Palliative care (PC) in lung transplantation is increasingly acknowledged for its important role in addressing symptoms, enhancing functionality, and facilitating advance care planning for patients, families, and caregivers. The present review provides an update in PC management in lung transplantation.

Recent findings: Research confirms the effectiveness of PC for patients with advanced lung disease who are undergoing transplantation, showing improvements in symptoms and reduced healthcare utilization. Assessment tools and patient-reported outcome measures for PC are commonly used in lung transplant candidates, revealing discrepancies between symptom severity and objective measures such as exercise capacity. The use of opioids to manage dyspnea and cough in the pretransplant period is deemed safe and does not heighten risks posttransplantation. However, the integration of PC support in managing symptoms and chronic allograft dysfunction in the posttransplant period has not been as well described.

Summary: Palliative care support should be provided in the pretransplant and select peri-operative and posttransplant periods to help support patient quality of life, symptoms, communication and daily function.

Purpose of review: Lung cancer remains the leading cause of cancer mortality worldwide. Health disparities have long been noted in lung cancer incidence and survival and persist across the continuum of care. Understanding the gaps in care that arise from disparities in lung cancer risk, screening, treatment, and survivorship are essential to guiding efforts to achieve equitable care.

Recent findings: Recent literature continues to show that Black people, women, and people who experience socioeconomic disadvantage or live in rural areas experience disparities throughout the spectrum of lung cancer care. Contributing factors include structural racism, lower education level and health literacy, insurance type, healthcare facility accessibility, inhaled carcinogen exposure, and unmet social needs. Promising strategies to improve lung cancer care equity include policy to reduce exposure to tobacco smoke and harmful pollutants, more inclusive lung cancer screening eligibility criteria, improved access and patient navigation in lung cancer screening, diagnosis and treatment, more deliberate offering of appropriate surgical and medical treatments, and improved availability of survivorship and palliative care.

Summary: Given ongoing disparities in lung cancer care, research to determine best practices for narrowing these gaps and to guide policy change are an essential focus of future lung cancer research.

Purpose of review: Infections in lung transplant recipients remain a major challenge and can affect lung allograft function and cause significant morbidity and mortality. New strategies for the prevention and treatment of infection in lung transplantation have emerged and are reviewed.

Recent findings: For important vaccine preventable infections (VPIs), guidance has been updated for at risk solid organ transplant (SOT) recipients. However, data on the efficacy of newer vaccines in lung transplant, including the respiratory syncytial virus (RSV) vaccine, are limited. Studies demonstrate improved vaccination rate with Infectious Diseases consultation during pretransplant evaluation. Two new antiviral agents for the treatment and prevention of cytomegalovirus (CMV) in SOT, letermovir and maribavir, are being incorporated into clinical care. CMV-specific cell-mediated immune function assays are more widely available. Antibiotics for the management of multidrug resistant pathogens and Burkholderia cepacia complex have been described in case series and case reports in lung transplant.

Summary: Although new vaccines and novel therapies for preventing and treating infections are available, larger studies evaluating efficacy in lung transplant recipients are needed.

Purpose of review: Early-stage nonsmall cell lung cancer (NSCLC) accounts for 30% of the total NSCLC, being the stage III a heterogeneous disease that represents a challenge in the management of these patients. Multidisciplinary approach is essential for an adequate treatment strategy, with surgery being the only curative treatment. Neoadjuvant or adjuvant chemotherapy has been the standard of care for a long period, with modest results.

Recent findings: Combination of chemotherapy and immunotherapy has revolutionized the neoadjuvant setting of resectable NSCLC, improving pathologic complete responses and survival outcomes in this scenario. Furthermore, perioperative treatment with immunotherapy has also recently shown promising results in several phase III trials.

Summary: The landscape of early-stage resectable NSCLC has evolved in recent years, with an improvement in the survival of these patients since the incorporation of immunotherapy in this scenario.