Pulmonary Therapy最新文献

Introduction: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma.

Methods: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants.

Results: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice.

Conclusions: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

Introduction: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS).

Methods: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants' descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants' ratings of strategies' effectiveness. Concept saturation was also assessed.

Results: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) were interviewed. At the time of the interview, 15 participants (75%) had received ALIS for > 1 month and 13 (65%) were currently receiving ALIS. Participants described 44 unique AE mitigation strategies, which can be categorized into three groups: prepare for treatment; prevent increased emergence of AEs; and persist on treatment by mitigating AEs. Common strategies (reported by ≥ 50% of participants) included use of educational materials from the patient support program, localized management of throat irritation, and symptom management to reduce fatigue. Evidence of concept saturation was observed: no new strategies were identified in the last five interviews, which suggests the sample was robust enough to identify all mitigation strategies likely to be used by the broader patient population.

Conclusions: This real-world study identified a diverse set of potential AE mitigation strategies intended to help individual patients prepare for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate the impact of AEs on treatment persistence. Developing a comprehensive accounting of the types of mitigation strategies in use among patients in real-world settings can inform future investigation of the effectiveness of such strategies, and support evidence-based recommendations for treatment management.

Introduction: Medical thoracoscopy is a minimally invasive and safe procedure mostly performed for unexplained exudative pleural effusions but may be considered for pneumothorax (PNX).

Methods: This retrospective study included participants affected by PNX who underwent medical thoracoscopy with talc poudrage at a single academic hospital from 2008 to 2021. The primary endpoint was the observation of complete radiographical lung re-expansion and absence of air supply from the chest drain within 7 days of medical thoracoscopy. The secondary endpoint was achieving no recurrence of ipsilateral PNX at 24 months post-discharge.

Results: A total of 95 patients affected by primary spontaneous PNX (PSP), secondary spontaneous PNX (SSP), iatrogenic, and traumatic PNX were enrolled. An additional procedure was required by 17.89% of patients, and only one patient with SSP required subsequent surgery. Recurrence of PNX occurred on the same side within 24 months after discharge in 9.47% of patients, with a median time to recurrence of 13.5 months. The PSP group was significantly more likely to achieve the primary endpoint. Pleural morphology was significantly associated with reaching the primary endpoint, while receiving a cumulative dose of talc greater than or equal to 4 g during hospitalization was associated with a lower risk of meeting it. Receiving a cumulative dose of talc greater than or equal to 4 g led in all cases to the achievement of the secondary endpoint. Patients with iatrogenic and traumatic PNX had an excellent prognosis in both the short- and long-term evaluation.

Conclusion: Medical thoracoscopy is an effective procedure for treating PNX in the acute setting in selected cases while preventing long-term relapses. Large prospective clinical studies are needed to support and better define the role of medical thoracoscopy in current clinical practice.

Introduction: Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis.

Methods: This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS).

Results: Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre ≥ 1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of ≥ 10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P = 0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P = 0.002].

Conclusion: IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA.

Trial registration: ClinicalTrials.gov identifier, NCT01366209.

Regardless of the type, extracorporeal membrane oxygenation (ECMO) requires the use of large intravascular cannulas and results in multiple abnormalities including non-physiologic blood flow, hemodynamic perturbation, rapid changes in blood oxygen and carbon dioxide levels, coagulation abnormalities, and a significant systemic inflammatory response. Among other sequelae, neurologic complications are an important source of mortality and long-term morbidity. The frequency of neurologic complications varies and is likely underreported due to the high mortality rate. Neurologic complications in patients supported by ECMO include ischemic and hemorrhagic stroke, hypoxic brain injury, intracranial hemorrhage, and brain death. In addition to the disease process that necessitates ECMO, cannulation strategies and physiologic disturbances influence neurologic outcomes in this high-risk population. For example, the overall documented rate of neurologic complications in the venovenous ECMO population is lower, but a higher rate of intracranial hemorrhage exists. Meanwhile, in the venoarterial ECMO population, ischemia and global hypoperfusion seem to compose a higher percentage of neurologic complications. In what follows, the literature is reviewed to discuss the pathophysiology, incidence, risk factors, and outcomes related to short-term neurologic complications in patients supported by ECMO.

This article is co-authored by five patients living with chronic obstructive pulmonary disease (COPD), and a primary care physician who has over 30 years of clinical experience and is involved in educating healthcare professionals. The first section of this article is authored by the patients, who describe their experiences of living with COPD. The section that follows is authored by the physician, who discusses the management of COPD in the context of the patients' experiences.

Introduction: The presence of antibiotic allergy labels can have harmful impacts on clinical outcomes, particularly among immunosuppressed patients, in whom there have been associations with increased complications, readmission rates, and mortality. We explore the effects of a sulfonamide allergy label (SAL) on clinical outcomes in adult patients with Pneumocystis jirovecii pneumonia (PJP).

Methods: In this retrospective matched cohort study, we utilized TriNetX, a multicenter national database, to match 535 adult patients with PJP and SAL to an equal number of controls. We identified cases indexed between 01/01/2010 and 01/01/2023 utilizing ICD-10 codes for PJP and allergy status to sulfonamides and through detection of P. jirovecii antigen with immunofluorescence or PCR. Propensity score matching was performed in a 1:1 fashion for demographics and comorbidities, and our analysis included clinical outcomes that occurred within 30 days after the occurrence of the index event.

Results: While hospitalization risk tended to be lower among patients with SAL as compared to controls (RR: 0.90; 95% CI 0.81-1.01), there were no major differences in the risk of respiratory failure (RR: 0.94; 95% CI 0.84-1.05), prednisone use (RR: 1; 95% CI 0.91-1.10), intensive level of care requirement (RR: 0.85; 95% CI 0.69-1.06), intubation (RR: 0.85; 95% CI 0.61-1.19), or mortality (RR: 0.98; 95% CI 0.68-1.42). The presence of SAL did however impact antibiotic prescription patterns, with an underutilization of trimethoprim (RR: 0.50; 95% CI 0.43-0.59) and sulfamethoxazole (RR, 0.47; 95% CI 0.40-0.56) and overuse of alternative agents by patients with SAL as compared to controls. Yet, there was no difference in the occurrence of adverse outcomes such as hepatotoxicity (RR: 1.09; 95% CI 0.49-2.45) or acute kidney injury (RR: 0.94; 95% CI 0.78-1.14) between patients with SAL and controls.

Conclusions: The presence of SAL alters antibiotic prescription patterns among adults with Pneumocystis infection but has no clinically significant impact on outcomes.

Introduction: Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This post hoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia.

Methods: The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1 s (FEV₁) and blood eosinophil count (BEC) was evaluated.

Results: This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50 years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63 years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5 kg/m², but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL).

Conclusions: There was little evidence of a differential effect of older age, lower BMI, lower FEV₁ and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD.

Clinical trial registration: IMPACT ClinicalTrials.gov number, NCT02164513.

The asthma pandemic imposes a huge burden on patients and health systems in both developed and developing countries. Despite available treatments, symptom control is generally suboptimal, and hospitalizations and deaths remain at unacceptably high levels. A pivotal aspect of asthma that warrants further exploration is the influence of the respiratory microbiome and virome in modulating disease activity. A plethora of studies report that the respiratory microbiome is characteristically dysbiotic in asthma. In addition, our data suggest that dysbiosis is also observed on the respiratory virome, partly characterized by the reduced abundance of bacteriophages (phages). Even though phages can naturally infect and control their bacterial prey, phage therapy has been grossly neglected in the Western world, although more recently it is more widely used as a novel tool against bacterial infections. However, it has never been used for tackling microbiome dysbiosis in human non-communicable diseases. This review provides an up-to-date understanding of the microbiome and virome's role within the airways in relation to asthma morbidity. It also advances the rationale and hypothesis for the CURE project. Specifically, the CURE project suggests that managing the respiratory microbiome through phage therapy is viable and may result in restoring eubiosis within the asthmatic airway. This entails controlling immune dysregulation and the clinical manifestation of the disease. To accomplish this goal, it is crucial to predict the effects of introducing specific phage mixtures into the intricate ecology of the airways and devise suitable interventions.

Introduction: Staphylococcus aureus (S. aureus) is an important pathogen in both community-acquired and hospital-acquired pneumonia. S. aureus pneumonia has a high mortality rate and serious complications. Resistance to multiple antibiotics is a major challenge in the treatment of S. aureus pneumonia. Understanding the antibiotic resistance profile of S. aureus and the risk factors for mortality can help optimize antibiotic regimens and improve patient outcomes in S. aureus pneumonia.

Methods: A prospective cohort study of 118 patients diagnosed with S. aureus pneumonia between May 2021 and June 2023 was conducted, with a 30-day follow-up period. Demographic information, comorbidities, Charlson Comorbidity Index, clinical characteristics, outcomes, and complications were collected for each enrolled case. The data were processed and analyzed using R version 3.6.2.

Results: S. aureus pneumonia has a 30-day mortality rate of approximately 50%, with complication rates of 22% for acute respiratory distress syndrome (ARDS), 26.3% for septic shock, and 14.4% for acute kidney injury (AKI). Among patients with methicillin-resistant S. aureus (MRSA) pneumonia treated with vancomycin (n = 40), those with a vancomycin minimum inhibitory concentration (MIC) ≤ 1 had significantly higher cumulative survival at day 30 compared to those with MIC ≥ 2 (log-rank test p = 0.04). The prevalence of MRSA among S. aureus isolates was 84.7%. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) criteria for severe pneumonia were significantly associated with mortality in a multivariate Cox regression model based on the adaptive least absolute shrinkage and selection operator (LASSO).

Conclusions: S. aureus pneumonia is a severe clinical condition with high mortality and complication rates. MRSA has a high prevalence in Can Tho City, Vietnam. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the IDSA/ATS criteria for severe pneumonia are risk factors for mortality in S. aureus pneumonia.