Pulmonary Therapy最新文献

Hepatic hydrothorax (HH) represents a distinct clinical entity within the broader classification of pleural effusion that is associated with significant morbidity and mortality. The median survival of patients with cirrhosis who develop HH is 8-12 months. The diagnosis is typically made in the context of advanced liver disease and ascites, in the absence of underlying cardio-pulmonary pathology. A multi-disciplinary approach to management, involving respiratory physicians, hepatologists, and palliative care specialists is crucial to ensuring optimal patient-centered care. However, the majority of accepted therapeutic options are based on expert opinion rather than large, adequately powered randomized controlled trials. In this narrative review, we discuss the epidemiology, pathophysiology, clinical characteristics, and management of HH, highlighting the use of salt restriction and diuretic therapy, porto-systemic shunts, and liver transplantation. We include specific sections focusing on the role of pleural interventions and palliative care, respectively.

Introduction: The disease origins of idiopathic pulmonary fibrosis (IPF), which occurs at higher rates in certain races/ethnicities, are not understood. The highest rates occur in white persons of European descent, particularly those with light skin, who are also susceptible to lysosomal organelle dysfunction of the skin leading to fibroproliferative disease . We had observed clinically that the vast majority of patients with IPF had light-colored eyes, suggesting a phenotypic characteristic.

Methods: We pursued this observation through a research database from the USA Veterans Administration, a population that has a high occurrence of IPF due to predominance of elderly male smokers. Using this medical records database, which included facial photos, we compared the frequency of light (blue, green, hazel) and dark (light brown, brown) eyes among white patients diagnosed with IPF compared with a control group of lung granuloma only (no other radiologic evidence of interstitial lung disease).

Results: Light eye color was significantly more prevalent in patients with IPF than in the control group with lung granuloma [114/147 (77.6%) versus 129/263 (49.0%], p < 0.001), indicating that light-colored eyes are a phenotype associated with IPF .

Conclusion: We provide evidence that light eye color is predominant among white persons with IPF.

Introduction: Available therapies for acute cough, a condition frequently caused by a viral upper respiratory tract infection (URTI), have shown limited evidence of efficacy. Gefapixant, a P2X3-receptor antagonist, has demonstrated efficacy and safety in studies of the treatment of refractory or unexplained chronic cough, but its efficacy for treating acute cough has not been previously studied.

Methods: This was a phase 2a, randomized, double-blind, placebo-controlled, parallel-group, pilot study. Healthy volunteers were randomized 1:1 to receive twice-daily gefapixant 45 mg or placebo and inoculated with human rhinovirus 16 to induce URTI and cough. Participants were observed while quarantined for 7 days after the start of treatment. The primary endpoint was awake cough frequency on day 3, which was objectively measured with a cough-recording device. Secondary endpoints included change from baseline to day 3 in subjective cough severity measures (cough severity visual analog scale, Cough Severity Diary) and cough-specific quality of life (Leicester Cough Questionnaire-acute).

Results: Of the 46 participants who met inclusion criteria [mean (standard deviation, SD) age, 24.6 (6.5) years; females, n = 8], 40 completed the study (gefapixant, n = 21; placebo, n = 19). There was no significant difference in awake cough frequency on day 3 between the gefapixant and placebo groups [least squares means, 2.4 versus 2.7 coughs per hour, respectively; mean difference (95% confidence interval, CI), -0.3 (-2.3, 1.7); P = 0.75]. There were no significant between-group differences for any of the secondary endpoints. Peak cough frequency was low and occurred later in the study than expected (days 4-5). The safety profile was consistent with that of previous studies of gefapixant.

Conclusion: Compared with placebo, gefapixant did not reduce the frequency or severity of acute cough secondary to induced URTI. Induced viral URTI produced mild symptoms, including lower cough frequency than observed in previous studies of patients selected for acute cough associated with naturally occurring URTI.

Trial registration: ClinicalTrials.gov, NCT03569033; EudraCT, 2017-000472-28; protocol number, MK-7264-013.

Introduction: Patients with chronic obstructive pulmonary disease (COPD) often have poor sleep quality and report a worsening of respiratory symptoms during night-time. However, current clinical guidelines for COPD management do not specifically consider nocturnal symptoms when recommending pharmacological treatment. This study aimed to better understand the burden of nocturnal symptoms in patients with COPD, and to evaluate the importance of nocturnal symptom control compared with daytime and overall symptom control.

Methods: Data were analyzed from the Adelphi Respiratory Disease Specific Programme, a point-in-time survey of physicians and their patients, conducted in the USA in 2019. Primary care physicians and pulmonologists who managed three or more patients with COPD per month were eligible for inclusion; eligible patients were ≥ 18 years old, with a physician-confirmed diagnosis of COPD.

Results: Surveys from 171 physicians and 800 patients were analyzed. Everyday symptoms were reported in 14% of patients. In total, 88% of patients reported daytime symptoms, and 74% of patients experienced nocturnal symptoms, with 7% reporting daily nocturnal symptoms. Patients experiencing nocturnal symptoms every day had the greatest impairment in their activity as per the Work Productivity and Activity Impairment questionnaire (mean total activity impairment, 66.9%; nocturnal symptoms once or twice a week, 41.1%; no nocturnal symptoms, 26.4%). Patients experiencing daily nocturnal symptoms also had the lowest quality of life (QoL) as per the EuroQoL 5-Dimension 3-Level score. Physicians reported prescribing therapy based on sustained 24-h symptomatic relief for the majority of patients (78%). They reported nocturnal symptom control as a factor in their choice of therapy for 38% of patients, and daytime symptom control as a reason for 61% of patients.

Conclusion: Daytime and nocturnal symptoms are common among patients with COPD. Frequency of nocturnal symptoms is related to a significant impairment in activity and health-related QoL.

Introduction: Augmentation therapy with plasma-derived α₁-proteinase inhibitor (A1PI) products is currently the only approved disease-specific therapy for α₁-antitrypsin deficiency (AATD), a genetic disorder associated with decreased levels of A1PI. Systemic trough levels of A1PI in plasma or serum are widely accepted as a biochemical efficacy endpoint in clinical trials for A1PI products.

Methods: Retrospective analyses utilizing data from three clinical studies in patients with AATD were conducted to evaluate the pharmacokinetic(s) (PK) and biochemical efficacy comparability of Aralast NP and two other A1PI augmentation therapies, Aralast and Prolastin. All three A1PI products were administered as either single or multiple 60 mg/kg intravenous infusions. PK and biochemical efficacy comparability analyses were conducted by evaluating antigenic and functional A1PI serum or plasma concentration data from each of the three studies.

Results: Comparable PK parameters were demonstrated between the three products for antigenic A1PI levels following a single infusion, with baseline-corrected and uncorrected geometric mean ratios for peak and systemic exposure ranging from 89.0% to 99.6%, with 90% confidence intervals within the 80-125% reference interval for bioequivalence. Biochemical efficacy comparability analyses of Aralast and Prolastin after multiple infusions at steady state showed geometric mean ratios for uncorrected and baseline-corrected antigenic and functional A1PI trough concentrations over weeks 8-11, and for individual weeks, that ranged from 75.8% to 106.6%, with the majority of the 90% confidence intervals falling either within the 80-125% interval or in proximity to it. Nonparametric superpositioning at steady state suggested that predicted trough concentrations for Aralast NP were comparable to the observed concentrations for Aralast and Prolastin.

Conclusion: These retrospective analyses provide robust evidence that Aralast NP has biochemical efficacy and PK comparable to that of Aralast and Prolastin, supporting the use of any of these A1PI products for the treatment of patients with AATD.

Trial registration numbers: ClinicalTrials.gov identifiers, NCT00242385 and NCT00396006.

Introduction: Correct inhaler technique is essential for the optimal delivery of inhaled medicines and the successfully management of respiratory conditions. The general practitioner (GP), the prescriber of inhaled medicines, plays a crucial role in educating patients on inhaler technique. However, in the real-world setting, there are barriers. For the GP, it is time and competence and for the patient, it is their ability to recognise inhaler technique as an issue and their ability to maintain correct inhaler technique over time. This study aimed to determine GPs' experience, skills and priority placed on inhaler technique and to identify factor(s) associated with inhaler technique competence.

Methods: This cross-sectional observational study design surveyed GPs' perspectives on inhaler use and preferences for inhaler prescribing within their practice setting. GP inhaler technique was assessed. GPs were recruited through an established network of GP practices. Data collected include (i) practice demographics, (ii) inhaler technique opinions and experience, (iii) inhaler prescribing preferences and (iv) inhaler education history data. Data were analysed descriptively and multivariate logistic regression modelling was used to explore the relationship between outcomes and GPs' ability to use devices correctly.

Results: A total of 227 GPs completed the inhaler survey. Sixty-three percent of GPs reported receiving previous inhaler education and 73.3% educated or checked their patients' inhaler technique; 64.5% felt they were somewhat competent in doing so. GPs who reported not demonstrating inhaler technique believed that a pharmacist or a practice nurse would do so. When prescribing new inhaler devices, GPs considered the disease being treated first and then patient's experience with inhalers; they often already have an inhaler preference and this was related to familiarity and perceived ease of use. For GPs, inhaler competence was not associated with their previous inhaler education or the priority placed on inhaler technique.

Conclusion: GPs do recognise the importance of inhaler technique in respiratory management but their technique can be better supported with regular educational updates to inform them about new inhalers and management practices and to support appropriate inhaler choices for their patients.

Introduction: Data collected through ongoing, state-based, cross-sectional health surveys could be used to better understand the contribution of respiratory symptoms to impaired health among the US adult population.

Methods: We used the 2015 Behavioral Risk Factor Surveillance System telephone health survey in four states (Kentucky, Florida, South Carolina, Texas) to describe the relationship between symptoms, associated factors such as tobacco smoking, and health impairments. Self-reported productive cough, shortness of breath (SOB), and dyspnea on exertion (DOE) were categorized as minimal, moderate, or severe. Data were analyzed using multiple logistic regression models with age as a covariate to assess relationships of symptoms with other factors.

Results: Among adults ≥ 18 years, respiratory impairment [current asthma, chronic obstructive pulmonary disease (COPD), or a current moderate or severe symptom] occurred in 39.1% of the population. More than half of adults reporting moderate or severe symptoms had not been diagnosed with asthma or COPD, particularly with DOE and productive cough. Subjects were at greater risk of moderate and severe SOB or productive cough with increasing age, prolonged smoking duration (≥ 20 years), being an ever-smoker, or if reporting COPD, current asthma, or any other comorbidity except cancer. Morbid obesity [body mass index (BMI) > 35 kg/m²] was associated with severe DOE at a rate similar to current asthma or COPD (25.6%, 95% CI 20.9-30.3%; 20.8%, 95% CI 16.4-25.1%; 21.3%, 95% CI 17.5-25.1%, respectively); it was the most common cause of DOE. SOB was associated with worse general health impairment and limited ambulation compared with other symptoms. Tobacco smoking prevalence and race varied among states, affecting symptom prevalence.

Conclusion: In the largest US survey in decades, we provide a current perspective of respiratory symptoms among adults of all ages. While known risk factors were apparent, low-risk persons also frequently reported symptoms and impairments.

Introduction: Single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy was approved by the United States Food and Drug Administration in 2017 as a maintenance therapy for chronic obstructive pulmonary disease (COPD). Patient characteristics and treatment patterns prior to initiating FF/UMEC/VI are currently unknown. This study assessed patient characteristics, exacerbation, and medication history in patients with COPD before the initiation of FF/UMEC/VI or multiple-inhaler triple therapy (MITT).

Methods: This was a retrospective study using the Optum Clinformatics^® Data Mart. Patients who initiated FF/UMEC/VI triple therapy or MITT (consisting of a long-acting muscarinic antagonist [LAMA], long-acting β2-agonist [LABA], and inhaled corticosteroid [ICS]) between October 2017 and September 2018, were enrolled in commercial or Medicare Advantage Prescription Drug plans, were aged > 40 years, and had a COPD diagnosis were eligible. Patient characteristics, comorbidities, COPD medication use, exacerbations, and eosinophil counts were assessed in the 12-month baseline period prior to initiation of FF/UMEC/VI triple therapy or MITT.

Results: The study population included 3933 FF/UMEC/VI users and 18,244 MITT users. Mean (standard deviation) patient age was 72.2 (8.6) years in FF/UMEC/VI users and 70.7 (9.7) years in MITT users. Prior to initiating triple therapy, the majority of FF/UMEC/VI (89.1%) and MITT (93.8%) users experienced a moderate or severe exacerbation or used a COPD maintenance therapy during the baseline period. In addition, 41.2% of FF/UMEC/VI users received overlapping ICS/LAMA/LABA, 20.3% received ICS/LABA, and 9.7% received LAMA/LABA.

Conclusion: In this population of COPD patients, triple therapy was frequently initiated after previous maintenance medication use or an exacerbation, in line with treatment guideline recommendations.

Cystic fibrosis (CF) is due to a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which leads to unusual water and chloride secretion across epithelial surfaces. The lungs are responsible for most morbidity, though other organs are frequently affected. Sleep abnormalities have long been recognized in CF. Abnormal ventilation and oxygenation, sinus disease, deconditioning due to muscle weakness and recurrent infections, and inflammation have been thought to play a role in sleep disorders in CF. However, there is evidence that CFTR gene dysregulation can affect circadian rhythms in CF. Early recognition and treatment of circadian rhythms may improve outcomes in CF.

The number of waitlisted lung transplant candidates exceeds the availability of donor organs. Barriers to utilization of donor lungs include suboptimal lung allograft function, long ischemic times due to geographical distance between donor and recipient, and a wide array of other logistical and medical challenges. Ex vivo lung perfusion (EVLP) is a modality that allows donor lungs to be evaluated in a closed circuit outside of the body and extends lung donor assessment prior to final acceptance for transplantation. EVLP was first utilized successfully in 2001 in Lund, Sweden. Since its initial use, EVLP has facilitated hundreds of lung transplants that would not have otherwise happened. EVLP technology continues to evolve and improve, and currently there are multiple commercially available systems, and more under investigation worldwide. Although barriers to universal utilization of EVLP exist, the possibility for more widespread adaptation of this technology abounds. Not only does EVLP have diagnostic capabilities as an organ monitoring device but also the therapeutic potential to improve lung allograft quality when specific issues are encountered. Expanded treatment potential includes the use of immunomodulatory treatment to reduce primary graft dysfunction, as well as targeted antimicrobial therapy to treat infection. In this review, we will highlight the historical development, the current state of utilization/capability, and the future promise of this technology.