People with asthma who overuse SABAs were enrolled into the study through community pharmacist invitation. Semi-structured interviews were completed by telephone or via Zoom. The recordings were transcribed and thematically analyzed using inductive and deductive approaches. Between September 2021 and May 2022, 21 people were interviewed. Data analyses yielded six themes. Three themes related to risk perception including risks related to asthma, medicines, and other factors such as environmental triggers. Three themes related to how people responded to their perceived risk. These included actions taken by some to reduce risk while others chose not to act to reduce risk, despite knowing how to, suggesting a lack of self-efficacy. This is the first study of its kind in a group of Australians who have asthma, a common, as yet incurable, often lifelong chronic health condition. Our interviews yielded rich and sometimes surprising insights into the complexity and number of factors contributing to how people perceive and respond to risks associated with their asthma and with the medicines that they take to manage it. Safer use of reliever medications - a matter of better risk communication by health professionals. The Asia-Pacific Society of Respirology Annual Conference; Singapore, November 2023.Short-acting beta2-agonist overuse is risky, but how do users with asthma perceive and respond to risk? Thoracic Society of Australia and New Zealand Annual Conference, Gold Coast, Australia, March 2024.
Objective: Preliminary analysis of dynamic expression characteristics of plasma proteins in children with allergic asthma during subcutaneous immunotherapy (SCIT) with dust mite allergens based on multi-time-point proteomics technology. Methods: A cross-sectional study was conducted, enrolling 84 children with allergic asthma primarily sensitized to house dust mites (HDM) who visited the Children's Hospital of Soochow University between November 2024 and May 2025. Participants were categorized into five groups based on the duration of SCIT: 0M, 3M, 6M, 12M, and 24M. To detect the levels of specific immunoglobulin E (sIgE) and specific immunoglobulin G4 (sIgG4) against dust mite components (Der p1, Der f1, Der p2, Der f2, Der p5, Der p7, Der p10, Der p21, Der p23). Five subjects were randomly selected from each group using simple random sampling, and an additional 5 healthy children (HC) were included as the control group for plasma proteomic analysis. The temporal expression patterns of differentially expressed proteins were clustered via the Mfuzz algorithm and subjected to functional annotation. Results: A total of 84 children were enrolled, with a mean age of (10.12±2.15) years, including 57 males and 27 females. Statistically significant differences were observed in Der p1-, Der f1-, Der p2-, and Der f2-specific IgG4 levels among the five groups (all P<0.05). The 24M group exhibited significantly higher levels of Der p1-, Der f1-, Der p2-, and Der f2-specific IgG4 compared with the 0M group [Der p1: 695.20 (57.85, 1 894.60) vs 44.35 (32.10, 51.10); Der f1: 70.15 (51.35, 1 141.03) vs 46.65 (35.30, 63.68); Der p2: 3 440.20 (892.20, 4 183.00) vs 66.85 (43.08, 189.98); Der f2: 2 015.50 (704.60, 2 523.10) vs 69.10 (45.80, 159.35), all P<0.05]. Enrichment analysis of differentially expressed proteins in each group using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database showed that: compared with the healthy control group, the 0M group exhibited upregulation of cholesterol metabolism and complement/coagulation cascades, and downregulation of cornified envelope formation and ECM-receptor interaction pathways. compared with the 0M group, the 3M group showed upregulation of ECM-receptor interaction and focal adhesion and downregulation of fatty acid metabolism. The 6M group showed upregulation of cell adhesion molecules and downregulation of cholesterol metabolism; the 12M and 24M groups showed upregulation of TGF-β and PI3K-Akt pathways. Fuzzy C-means clustering analysis revealed that proteins highly expressed in the 6M group were enriched in glutathione metabolism, while those in the 24M group were significantly enriched in B cell-mediated immune responses. Six potential regulatory proteins (ARPC3, LPL, ILF3, FARSB, USP14, and SLIT2) were initially identified. Furthermore, Spearman correlation analysis revealed that ARPC3 was significantly negatively correlated with the levels of Der f2-sIgE, Der p2-sIgG4, and Der f2-sIgG4 (r=-0.44, -0.57, -0.54, respectively, all P<0.05). Additionally, ILF3 was positively correlated with Der p21-sIgE (r=0.57, P<0.01), FARSB was negatively correlated with Der p2-sIgG4 (r=-0.44, P<0.01), and USP14 was negatively correlated with Der f1-sIgE (r=-0.46, P<0.05). Conclusions: Differences exist in allergen antibody and plasma protein expression profiles among children with allergic asthma across groups with different durations of SCIT. The differentially expressed proteins may be involved in pathways related to airway epithelial barrier, metabolic homeostasis and immune regulation. 目的： 基于多时间点蛋白组学技术，初步分析过敏性哮喘儿童接受尘螨皮下特异性免疫治疗（SCIT）过程中血浆蛋白的动态表达特征。 方法： 本研究为横断面研究，纳入2024年11月至2025年5月就诊于苏州大学附属儿童医院的84例以屋尘螨为主要过敏原的过敏性哮喘儿童，按SCIT治疗时长分为0M、3M、6M、12M、24M组。检测尘螨组分（Der p1、Der f1、Der p2、Der f2、Der p5、Der p7、Der p10、Der p21、Der p23）特异性免疫球蛋白E（sIgE）与特异性免疫球蛋白G4（sIgG4）水平。每组经简单随机抽样直接抽选方法抽取5例，另设5名健康儿童为健康对照（HC）组进行血浆蛋白组学分析，差异蛋白的时间序列表达模式通过Mfuzz算法聚类分析，并进行功能注释和相关性分析。 结果： 纳入84例儿童，总体年龄为（10.12±2.15）岁，男57例，女27例。5组间尘螨组分Der p1、Der f1、Der p2、Der f2-sIgG4差异均有统计学意义（均P<0.05）。24M组Der p1、Der f1、Der p2、Der f2-sIgG4水平均高于0M组，差异均有统计学意义［Der p1∶695.20（57.85，1 894.60）比44.35（32.10，51.10）；Der f1∶70.15（51.35，1 141.03）比46.65（35.30，63.68）；Der p2∶3 440.20（892.20，4 183.00）比66.85（43.08，189.98）；Der f2∶2 015.50（704.60，2 523.10）比69.10（45.80，159.35），均P<0.05］。各组差异蛋白采用京都基因及基因组百科全书（KEGG）通路数据库富集分析显示：与HC相比，0M组胆固醇代谢、补体和凝血级联反应通路上调，细胞外基质-受体相互作用通路下调。与0M组相比，3M组细胞外基质-受体相互作用、黏着斑通路上调、脂肪酸代谢下调；6M组细胞黏附分子相互作用通路上调、胆固醇代谢下调；12M和24M组转化生长因子-β（TGF-β）、磷脂酰肌醇3-激酶/蛋白激酶B信号通路（PI3K-Akt）上调。时间序列聚类分析6M组高表达蛋白富集于谷胱甘肽代谢通路；24M高表达蛋白显著富集于B细胞介导免疫反应过程。初步筛选出6种潜在调控蛋白：肌动蛋白相关蛋白2/3复合物亚基3（ARPC3）、脂蛋白脂肪酶（LPL）、白细胞介素增强子结合因子3（ILF3）、苯丙氨酰-tRNA合成酶亚基β（FARSB）、泛素特异性蛋白酶14（USP14）、轴突导向因子SLIT2，且通过Spearman相关性分析发现ARPC3与Der f2-sIgE、Der p2-sIgG4、Der f2-sIgG4水平呈显著负相关（r分别为-0.44、-0.57、-0.54，均P<0.05）。ILF3与Der p21-sIgE水平呈显著正相关（r=0.57，P<0.01），FARSB与Der p2-sIgG4呈显著负相关（r=-0.44，P<0.01），USP14与Der f1-sIgE呈显著负相关（r=-0.46，P<0.05）。 结论： 不同SCIT治疗时长组间的过敏性哮喘儿童过敏原抗体及血浆蛋白表达谱存在差异，差异蛋白可能参与气道上皮屏障、代谢稳态及免疫调节相关通路。.
Geriatric rehabilitation reduces mortality and long-term care home (LTCH) admission. However, cognitive impairment is often perceived to be a barrier for successful rehabilitation. Our objective was to determine the impact of cognitive impairment on rehabilitation outcomes using a systematic review of inpatient geriatric rehabilitation. We conducted a secondary analysis of a recent systematic review and meta-analysis of geriatric rehabilitation in the inpatient settings. We screened 29 randomized controlled trials (RCTs) included in the original systematic review for those that reported rehabilitation outcomes (e.g. mortality, LTCH admission) by cognitive status (high vs. low cognition as defined by score cutoff or dementia diagnosis). Results were analyzed by (i) a meta-analysis of outcomes in those with cognitive impairment and (ii) pooling the within study interaction by cognitive status. Of 29 RCTs, 8 RCTs (1134 patients) reported outcomes by cognitive status. For the subgroup of patients with cognitive impairment, the risk ratio (RR) of mortality at the longest follow up was 0.75 (95% confidence interval [CI] 0.39 to 1.45, I2 = 61.0%) and the RR of LTCH admission was 0.89 (95% CI 0.62 to 1.28, I2 = 0). There was no interaction between baseline cognitive status and mortality (pooled interaction of difference in logRR - 0.12, 95% CI -0.72 to 0.48) or LTCH admission (pooled interaction 0.17, 95% CI -0.34 to 0.68). There is no interaction between baseline cognitive status and the outcomes in this systematic review, suggesting that baseline cognitive impairment does not alter the mortality and institutionalization benefits of geriatric rehabilitation. PROSPERO: CRD42022345078.
Individuals with Ehlers-Danlos Syndromes (EDS) and Generalized Hypermobility Spectrum Disorder (G-HSD) experience psychological distress and are at an increased risk for suicidal behaviors. The current study examined associations between factors uniquely relevant to this population and prior suicide attempts and non-suicidal self-injury (NSSI). Data were from a retrospective chart review of 394 consecutive patients (89% female) referred for an EDS/G-HSD assessment at the GoodHope EDS Clinic at Toronto General Hospital between November 2019 and June 2021. Patients completed suicide and self-injury screening questions prior to assessment, and analyses include those who did and did not receive a diagnosis. One in six reported a past suicide attempt (17.8%) and almost a third reported past NSSI (30.2%). Rates of NSSI and past suicide attempt did not differ based on EDS/G-HSD diagnosis. Separate adjusted logistic regression analyses revealed that joint hypermobility (aOR = 1.13, p = .037) and symptoms of borderline personality disorder (BPD) were associated with increased odds of reporting NSSI (aOR = 2.87, p < .001) and that BPD symptoms (aOR = 2.32, p < .001) and autonomic dysfunction (aOR = 1.06, p = .005) were associated with increased odds of reporting a past suicide attempt. Joint hypermobility, BPD symptoms, and autonomic dysfunction may be important factors when examining rates of NSSI and suicide attempts among individuals being assessed for EDS/G-HSD. Given the high prevalence of NSSI and suicide attempts observed, future research should continue to investigate mechanisms and examine the effectiveness of psychological interventions for this population.
In patients with refractory generalized myasthenia gravis (MG) inadequately controlled by standard immunotherapies, including intravenous immunoglobulin and intravenous methylprednisolone, molecular targeted therapies have emerged as important treatment options. Although both neonatal Fc receptor (FcRn) inhibitors and complement C5 inhibitors have demonstrated efficacy in anti-acetylcholine receptor antibody-positive generalized MG, the clinical utility of their combined use remains unclear. Here, we report two cases of refractory anti-acetylcholine receptor antibody-positive generalized MG successfully managed with combined FcRn and C5 inhibition. In Case 1, disease control was not achieved despite thymectomy, multiple standard immunotherapies, and FcRn inhibition alone. Sequential treatment with C5 inhibitors, including eculizumab, ravulizumab, and zilucoplan, was attempted; sustained stabilization occurred only after combination therapy with zilucoplan and subcutaneous efgartigimod. In Case 2, standard therapies were ineffective, and thymectomy under general anesthesia was considered unsafe because of severe disease activity. Combination therapy was therefore introduced to stabilize the disease and enable safe perioperative management. Following successful thymectomy, targeted therapies were discontinued in Case 2, whereas Case 1 required ongoing treatment. To our knowledge, this is one of the first reports demonstrating effective disease control using combined FcRn and C5 inhibition in refractory generalized MG. These cases suggest that this strategy may benefit selected patients with refractory disease, particularly when stable disease control is required; however, further studies are warranted to determine its broader applicability and long-term safety.
No recommended therapy exists for chronic fibrosing interstitial lung diseases (CF-ILD) with disease progression despite ongoing treatment with nintedanib or pirfenidone. Pamufetinib (also known as TAS-115) is a novel oral antifibrotic tyrosine kinase inhibitor in development for CF-ILD with a progressive phenotype. We sought to evaluate the dose-response of pamufetinib monotherapy in patients with CF-ILD including idiopathic pulmonary fibrosis (IPF) with a progressive phenotype despite an antifibrotic treatment. In this double-blind, multicenter, active-controlled phase 2 b study, patients with CF-ILD with a progressive phenotype (defined as ≥ 5% decline in the annual percent predicted forced vital capacity [%FVC] despite treatment with nintedanib or pirfenidone and an %FVC ≥ 50%) were randomized 1:1:1 to pamufetinib 50 mg, 100 mg, or control (nintedanib or pirfenidone) for ≥ 26 weeks. The primary endpoint was the 26-week rate of decline in FVC. Of the 243 patients randomized, approximately 70% had IPF. The 26-week rate of change in FVC was -157.8 mL, -95.9 mL, and -63.6 mL in patients receiving pamufetinib 100 mg, pamufetinib 50 mg, and control, respectively; as such, no clear dose-response relationship was observed. The most frequent adverse event in the pamufetinib groups was rash, which was mostly mild or moderate in severity. While the safety profile was acceptable, pamufetinib failed to decelerate FVC decline in patients with CF-ILD with a progressive phenotype who had previously been treated with nintedanib or pirfenidone. No benefits were demonstrated by switching from standard antifibrotic treatment to pamufetinib monotherapy.Clinical trial registered with the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/en-top; jRCT2051210050).
We tested the respective effect of high-flow and supplemental O2 from nasal high-flow O2 therapy (NHFO2) on dyspnea and exercise tolerance in fibrotic interstitial lung disease. Supplemental O2 and NHFO2 (but not high-flow) provided improvements in these outcomes at "iso-O2 saturation" due to reduced ventilatory requirements. Physiological benefits derived from O2 supplementation are thus likely primary drivers of dyspnea relief and improved exercise tolerance on NHFO2 (vs air) in these patients. Severe hypoxemia, heightened dyspnea, and exercise limitation are hallmarks of fibrotic interstitial lung disease (f‐ILD). Standard O2 therapy (nasal prongs) fails, however, to correct hypoxemia with limited symptomatic benefits due to inspiratory flow‐patient demand mismatch. Nasal high‐flow O2 therapy (NHFO2) is a promising alternative, but the respective contribution of high‐flow and supplemental O2 to improved dyspnea and exercise tolerance remains unknown in f‐ILD. Sixteen patients performed, in a randomized order, endurance tests (70% peak power) under 4 conditions: air, supplemental O2 (face mask, 9–12 L·min−1), NHFair [50–70 L·min−1; inspired fraction of O2 (FiO2) = 0.21], NHFO2 (50–70 L·min−1; FiO2 = 0.5). Endurance time and O2 saturation (SpO2), breathing pattern (respiratory plethysmography) and dyspnea (Borg CR‐10) were compared across conditions. Supplemental O2 (98 [2]%) and NHFO2 (99 [3]%) increased isotime SpO2 vs air (87 [17]%, p < 0.001). Exercise time improved on O2 and NHFO2 vs air and NHFair (683[903], 690[1338], 346[247], 319[415]s, respectively, p < 0.001; O2 vs NHFO2, p = 0.117). Supplemental O2 and NHFO2 reduced isotime ventilation vs air (47 ± 22, 44 ± 20, 63 ± 29 L·min−1, p < 0.001), driven by lower respiratory rates (36 ± 9, 37 ± 8, 44 ± 10 br·min−1, p < 0.001). Supplemental O2 and NHFO2 reduced isotime dyspnea vs air (4[3.5], 3.5[2.5], 7 [3], p < 0.001) and NHFO2 vs NHFair (3.5[2.5] vs 6[1.5], p = 0.016). NHFair lowered isotime ventilation (9.0 ± 6.2 L·min−1, p = 0.012) but did not improve dyspnea and exercise time vs air. Supplemental O2 and NHFO2 improved dyspnea and exercise time at “iso‐O2 saturation” in severely hypoxemic f‐ILD. Physiological benefits from supplemental O2 (including lower ventilation) are thus likely primary drivers of dyspnea relief and improved exercise tolerance on NHFO2 vs air in f‐ILD. NCT07129707 (registered at ClinicalTrials.gov).
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To demonstrate our endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) results and review in detail the recommendations of the American College of Chest Physicians (ACCP) guidelines and local clinical practice at a tertiary Thoracic Oncology center. Consecutive patients diagnosed with non-small cell lung cancer (NSCLC) between September 2008 and December 2017 who underwent EBUS-TBNA of mediastinal and hilar lymph nodes (LNs) for diagnosis and staging were enrolled. Systematic LN staging was performed. All patients were classified into 2 groups on the basis of the ACCP guidelines. Patients with clinical N0 (cN0) and peripheral NSCLC measuring 3 cm or less, for whom LN staging is not recommended, were classified into group A (n = 43). Patients with cN1-3, central, and/or NSCLC measuring more than 3 cm, for whom LN staging is recommended, were classified into group B (n = 626). In total, 669 patients were included. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of LN staging were 85.0%, 100%, 100%, 84.7%, and 91.8%, respectively. In total, 11% of group A patients had N2 disease and 4% had N3 disease; however, only 1 of these cases was detected using EBUS-TBNA. Occult N2 disease is common in patients diagnosed as cN0 with peripheral <3 cm NSCLC. Further studies are needed to evaluate patient and tumor characteristics associated with occult LN metastasis in this patient population. Nevertheless, careful consideration should be given to the potential presence of LN metastasis within group A.
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Ocular manifestations rarely represent the first sign of systemic malignancy and often pose a diagnostic challenge. While choroidal metastases are more common, iris involvement is uncommon and may be underrecognized. Lung adenocarcinoma, particularly non-small cell subtypes, is a known source of ocular metastases, with iris lesions occasionally preceding systemic symptoms. We report a 70-year-old previously healthy man presenting with one month of left eye blurred vision. Initial examination revealed conjunctival injection and visual acuity of 6/20 without detectable lesions; topical dexamethasone was prescribed. Six weeks later, vision declined to finger counting, and a hypopigmented iris mass (7.0 × 5.7 mm) was identified. A brain MRI revealed a right occipital lesion, and a CECT of the thorax, abdomen, and pelvis showed a left lung mass with bilateral nodules, mediastinal lymphadenopathy, and right iliac metastasis. CT-guided biopsy confirmed stage IV lung adenocarcinoma (TTF-1 and Napsin A positive, PD-L1 TPS 80%, EGFR/ALK/ROS1 negative). Pembrolizumab was initiated; filamentous keratitis developed during therapy, and progression at three months prompted conventional chemotherapy. This case emphasizes the rarity of iris metastasis as the initial presentation of lung adenocarcinoma.
We previously built and validated the Electronic Asthma Management System (eAMS)-a clinic-based asthma computerized clinical decision support system (CDSS) which is in clinical use. Herein, we sought to adapt and optimize the eAMS for implementation in community pharmacy practice. We iteratively developed a system prototype (the eAMS-Pharm) with input from clinical pharmacists, and asthma, knowledge translation, and eHealth experts. After face-validation by three external community pharmacists, we used a rapid-cycle development process for optimization of system design (format), content, and user workflows (usability). This involved a sequential and repeated three-stage process: (1) system prototype demonstration and testing in 90 min, semi-structured virtual focus groups with target end-users; (2) analysis of focus group findings; and (3) corresponding modifications to the prototype, then re-testing in another focus group. This process continued until we reached pre-defined stopping criteria. We used a questionnaire to gather demographic information and further usability data and feedback. Community pharmacy team members were recruited from an existing pharmacy database. Stopping criteria were met after six focus group cycles with 28 participants [23 (83%) pharmacists, 4 (14%) registered pharmacy technicians/assistants, and 1 (3%) pharmacy student]. User feedback and corresponding system improvements spanned usability, workflow, and prescriber communication domains. The optimized system consisted of a pharmacy portal with a patient dashboard, patient and provider versions of a point-of-care questionnaire, an interactive CDSS producing guideline-based recommendations, automated documentation, and pre-formatted prescriber communications. The System Usability Scale score was 82.9 ± 16.8 (maximum 100), and user responses to Likert scale-based assessments of eAMS-Pharm design, content, workflow, impact, and overall impressions were highly favorable. We built and optimized a chronic disease CDSS for use in community pharmacies, identifying and addressing pharmacy-specific barriers to implementation. The system achieved a high system usability score and highly favorable ratings for perceived system benefits, likelihood of clinical use, and patient benefits. The eAMS-Pharm can now be evaluated for uptake, care impact, and outcome impact in real-world settings. Our findings surrounding users' design, content, and usability/workflow preferences, and our unique development strategy, can also inform future pharmacy-based chronic disease CDSS design.
Physical inactivity contributes to adverse health outcomes and is particularly detrimental in respiratory diseases. Despite being promoted as safer cigarette alternatives, the behavioural effects of heated tobacco products (HTPs) on physical activity remain unclear. This study examined the association between HTP use and physical activity among Japanese adults, particularly those with respiratory diseases. A cross-sectional study used data from the 2023 Japan COVID-19 and Society Internet Survey (JACSIS), including 28,353 participants aged ≥ 15 years. Tobacco use was classified as never, current, or former use of cigarettes and/or HTPs. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) and expressed in MET-min/week. Multivariable analyses applied analysis of covariance (ANCOVA) and logistic regression comparing low versus moderate/high physical activity, adjusting for demographic, behavioural, and health factors. Predicted means of physical activity from the ANCOVA model were 1100.9 for never smokers, 1006.8 for cigarette smokers, and 945.6 MET-min/week for HTP users. Current cigarette smokers (β = -94.1 [95% CI: -176.7 to -11.5], p = 0.026) and current HTP users (β = -155.3 [95% CI: -252.7 to -57.9], p = 0.002) exhibited significantly lower physical activity than never smokers. Sensitivity analyses using log-transformed IPAQ scores and logistic regression confirmed these findings. Subgroup analyses indicated reduced activity among HTP users with asthma, but no clear pattern for COPD. Cigarette smoking and HTP use were associated with lower physical activity, independent of confounders. Smoking cessation, particularly in asthma, should be prioritized, alongside promoting physical activity among tobacco users.
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To describe clinical characteristics and post-lung transplant outcomes of patients with idiopathic inflammatory myopathies (IIM),systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). We retrospectively analyzed interstitial lung disease (ILD) patients with IIM (n = 22), SSc (n = 32), and IPF (n = 64) who underwent lung transplantation (2012-2024) at two Canadian centers, Vancouver and Montréal. Among IIM patients, 41% was clinically amyopathic at presentation, and 45% had anti-MDA5 dermatomyositis (DM), all with rapid progressive (RP)-ILD, 32% anti-synthetase syndrome, 14% overlap myositis, and 9% other DM. In SSc, 88% had pulmonary hypertension (PH) (31% severe) and 78% had esophageal dysmotility. IIM patients required more frequent pre-transplant ICU admission and emergency transplantation. Post-transplant, IIM patients had longer ICU/hospital stays. There were no significant differences in 1-year survival, survival at last follow-up (median: 2.8 years for IIM, 2.5 years for SSc, and 3.6 years for IPF), incidence of chronic lung allograft dysfunction, or malignancy. Subgroup analyses of IIM (stratified by transplant urgency, extracorporeal membrane oxygenation (ECMO) support, and amyopathy) and SSc (stratified by severe PH, esophageal dysmotility, and transplant urgency) showed no significant differences in long-term survival. No autoimmune disease recurrence was observed. Despite their underlying autoimmune diseases, post-transplant survival outcomes of selected IIM and SSc patients did not differ significantly from those with IPF. IIM patients with RP-ILD necessitating emergency transplantation and ECMO support exhibited survival similar to those without such complications. However, their more complex pre- and post-transplant courses emphasize the necessity for individualized lung transplant strategies and a multidisciplinary management approach.
Pneumocystis jirovecii pneumonia (PCP) remains a life-threatening opportunistic infection in patients receiving chemotherapy and other immunosuppressive cancer treatments. Accurate identification of true PCP cases within real-world electronic health record (EHR) databases is essential for epidemiological research and optimization of prophylactic strategies in oncology practice. The aim of this study was to develop and validate a practical, EHR-based algorithm for reliably identifying PCP cases. This retrospective, single-center validation study used EHR data from a Japanese university hospital between April 2022 and March 2024. Adult patients (≧20 years) who were assigned an ICD-10 code for PCP were extracted, and true cases were confirmed by a detailed review of the patient records. Seven candidate algorithms combining diagnostic codes, therapeutic-dose anti-PCP prescriptions, laboratory testing, chemotherapy exposure, and prescription duration were evaluated. The positive predictive value (PPV) and capture rate were then calculated using chart-confirmed PCP as the reference standard. Among 617 ICD-coded patients, 11 (1.8%) were confirmed as true PCP cases. The PPV of diagnostic codes alone was 1.8%. A prescription-enhanced algorithm (A1) identified 12 patients, including 11 true cases (PPV=91.7%; capture rate 100%). Algorithms incorporating β-D-glucan or PCR testing achieved PPVs of 100% with lower capture rates (63.6-81.8%). Incorporation of concurrent chemotherapy also resulted in a PPV of 100% with reduced capture. An algorithm requiring therapeutic-dose prescription for ≥21 days showed equivalent performance to A1. Prescription-based algorithms substantially improve the accuracy of PCP case identification in EHR data compared with diagnostic codes alone. This straightforward, scalable approach offers a robust framework for real-world oncology research, enabling a more reliable evaluation of PCP incidence and informing future prophylaxis strategies for patients receiving anticancer treatment.
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Elexacaftor/tezacaftor/ivacaftor (ETI) has demonstrated significant improvements in lung function, body mass index (BMI), symptom control, and health-related quality of life (HRQoL) in individuals with cystic fibrosis (CF). However, real-world evidence regarding its long-term impact on HRQoL, particularly in people without significant lung function improvement, remains limited. This study aimed to (1) assess HRQoL changes across multiple domains in individuals initiating ETI and (2) explore the relationship between clinical outcomes and HRQoL, particularly in those who do not experience a significant improvement in lung function. We conducted a prospective cohort study of adults initiating ETI at CF clinics across Canada. HRQoL was assessed using the Cystic Fibrosis Questionnaire-Revised (CFQ-R), Cystic Fibrosis Quality-of-Life Evaluative Self-Administered Test (CF-QUEST), and Sino-Nasal Outcome Test (SNOT-22) at baseline and at 3, 6, 9, and 12 months post-initiation. Lung function (percent predicted forced expiratory volume in 1 s [ppFEV1]) and BMI were also monitored. Individuals were classified as lung function responders (≥5% increase in ppFEV1) or non-responders (<5% increase). Among 353 individuals, significant improvements in CFQ-R, CF-QUEST, and SNOT-22 scores were observed within one month of ETI initiation and sustained over 12 months. Notably, both lung function responders and non-responders experienced significant HRQoL improvements, with no evidence of a difference between groups in terms of mean changes in CFQ-R respiratory scores (28.8 vs. 24.2, p = 0.2), CF-QUEST global scores (14.8 vs. 13.0, p = 0.48), or SNOT-22 scores (-13.8 vs. -13.7, p = 0.97). Our real-world data involving a large cohort of PwCF demonstrate that HRQoL improvements are sustained across multiple domains regardless of lung function response. These findings underscore the importance of using a multimodal approach to evaluate the effectiveness of modulator therapy in people with CF.
Exposure to ambient particulate matter ≤2.5 μm (PM2.5) is associated with lung function impairment, particularly in children. However, the impact of prenatal PM2.5 exposure on childhood airway mechanics remains unclear. We aimed to assess associations between prenatal PM2.5 exposure and airway mechanics in school-age children. Data from 1324 singleton children (745 boys, 56.3%; mean age, 6.5 years) participating in a population-based cohort in Taiwan were analysed. Prenatal ambient PM2.5 exposure near residence was estimated using hybrid kriging-land use regression models with an XGBoost algorithm. Airway mechanics were measured by impulse oscillometry. Each 10 μg/m3 increase in prenatal PM2.5 exposure across the entire pregnancy was associated with higher total airway resistance (R5: β, 0.67; 95% CI, 0.30-1.03), proximal airway resistance (R20: β, 0.37; 95% CI, 0.12-0.62), peripheral airway resistance (R5-R20: β, 0.30; 95% CI, 0.05-0.55), and airway impedance (Z5) (β, 0.58; 95% CI, 0.21-0.94). Distributed lag nonlinear models identified sensitive windows during late pregnancy: 30-34 gestational weeks for R5, 30-34 gestational weeks for Z5, and at 26-33 gestational weeks for AX, respectively. Stratified analyses indicated stronger associations in girls, children exposed to prenatal environmental tobacco smoke, and those not breastfed. Higher prenatal PM2.5 exposure, particularly during late pregnancy, may be associated with adverse changes in airway mechanics in school-age children, especially girls, children exposed to prenatal environmental tobacco smoke, and those not breastfed, highlighting the importance of minimizing PM2.5 exposure during late pregnancy to protect long-term respiratory health.