Increased exacerbations of bronchiectasis following recovery from mild COVID-19 in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Respiratory viral infection is a common trigger of bronchiectasis exacerbation. Knowledge of the intermediate to long-term effect of COVID-19 on bronchiectasis is poor. METHODS: A retrospective cohort study of patient records was conducted to assess the frequency of bronchiectasis exacerbation following recovery from mild-to-moderate COVID-19. The exacerbation frequency at baseline, using 2019 and 2019-2021 data, was compared with that during the 1 year following recovery. RESULTS: A total of 234 adult patient records who had a confirmed diagnosis of bronchiectasis were identified, of whom 52 (22.2%) were classified as the COVID-19 group. Patients with COVID-19 had significantly more frequent annual exacerbations of bronchiectasis (total exacerbations and hospitalizations). Compared with 2019-2021 data, the total exacerbation frequency decreased by 0.1 ± 0.51 per year among non-COVID-19 patients but increased by 0.68 ± 1.09 per year among the COVID-19 group (p < 0.001). Compared with 2019 only data, exacerbation frequency decreased by 0.14 ± 0.79 per year among non-COVID-19 patients but increased by 0.76 ± 1.17 per year in the COVID-19 group, p < 0.001. The annual frequency of hospitalization for bronchiectasis increased by 0.01 ± 0.32 per year among non-COVID-19 patients and increased by 0.39 ± 1.06 per year in the COVID-19 group (p < 0.001) compared with 2019 to 2021 data. When compared with only 2019 data, it remained unchanged at 0 ± 0.43 per year among non-COVID-19 patients but increased to 0.38 ± 1.12 per year among COVID-19 patients (p < 0.001). CONCLUSION: Mild-to-moderate COVID-19 was associated with an increase in frequency of bronchiectasis exacerbation and frequency of hospitalizations following recovery.

Worsening of asthma control after recovery from mild to moderate COVID-19 in patients from Hong Kong.

BACKGROUND: While there are postulations that asthma is potentially associated with severe coronavirus disease 2019 (COVID-19), there has been conflicting results from studies on the impact mild-to-moderate COVID-19 on asthma control after recovery. METHODS: A case control study on the association between mild-to-moderate COVID-19 and asthma control post infection was conducted. The primary outcome was a reduction in Asthma Control Test (ACT) score by ≥ 3 points post-COVID infection. The secondary outcomes included the change in ACT score, the proportion of patient with ACT score who dropped to ≤ 15 on enrolment visit and the need for escalation of asthma maintenance therapy. RESULTS: Out of the total of 221 adult patients with asthma recruited, 111 had mild-to-moderate COVID-19 within 30 to 270 days prior to study enrolment. The adjusted odds ratio (aOR) for a reduction in ACT score by ≥ 3 points after COVID-19 was 3.105 (95% CI = 1.385-6.959, p = 0.006). The odds of escalation of asthma maintenance therapy by at least 1 Global Initiative for Asthma (GINA) step was 4.733 (95% CI = 1.151-19.467, p = 0.031) and asthma patient are more likely to become uncontrolled after COVID-19 [aOR = 5.509 (95% CI = 1.061-28.600, p = 0.042)]. CONCLUSION: Mild-to-moderate COVID-19 among asthma patients, upon recovery, was associated with worsening of asthma symptom, lower ACT score, a higher need for escalation of asthma maintenance therapy and more uncontrolled asthma.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

Association of genetic polymorphisms of CYP3A4 and CYP2D6 with gefitinib-induced toxicities.

Dermatological, gastrointestinal and hepatic toxicities are the most common adverse events associated with gefitinib use. Gefitinib is metabolized by cytochrome P450. Inconsistent associations of single nucleotide genetic polymorphisms of CYP450 and gefitinib-induced adverse effects were reported. We aim to investigate the association between CYP450 genetic polymorphism and the development of gefitinib-associated adverse events. A retrospective cohort study of Chinese patients with metastatic nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations who received first-line gefitinib treatment was conducted. Single nucleotide polymorphisms (SNPs) of CYP2D6, CYP3A4 and CYP3A5 were assayed using a multiplex SNP microarray. Risks of development of gefitinib-induced toxicities associated with different SNPs were determined. Among the 152 patients treated with gefitinib, 52 (34.2%) had gefitinib-induced hepatotoxicity, 113 (74.3%) had cutaneous reactions and 53 (34.9%) had gastrointestinal adverse effects. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes were significantly associated with hepatic, cutaneous and gastrointestinal adverse effects [odds ratio (OR) 3.773; (95% confidence interval {CI},1.046-13.610; P = 0.043), 3.368 (95% CI, 1.000-11.345; P = 0.050) and 20.000 (95% CI, 2.381-167.965; P = 0.006), respectively]. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes may be associated with increased risks of gefitinib-induced toxicities in the liver, skin and gastrointestinal tract.

Validation of diagnostic coding for interstitial lung diseases in an electronic health record system in Hong Kong.

OBJECTIVE: Large electronic medical record (EMR) databases can facilitate epidemiology research into uncommon diseases such as interstitial lung disease (ILD). Given the rarity and diagnostic difficulty of ILD, the validity of the coding in EMR requires clarification. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying ILD in the territory-wide electronic medical health record system of Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. METHOD: Patients who visited the Queen Mary Hospital in 2005-2018 with ILD were identified using the following ICD-9 codes: post-inflammatory pulmonary fibrosis (PPF; ICD-9: 515), idiopathic fibrosing alveolitis (IFA; ICD-9: 516.3), connective tissue disease-associated interstitial lung disease (CTD-ILD; ICD-9: 517.2, 517.8, 714.81), sarcoidosis (ICD-9: 135) and extrinsic allergic alveolitis (EAA; ICD-9: 495). A random selection was conducted in cases with diagnostic code of PPF and IFA, where a relative higher case number was identified. All the cases of CTD-ILD, sarcoidosis and EAA were included in validation for relatively small case number. RESULTS: Two hundred and sixty nine cases were validated using medical record review by a respiratory specialist. The overall positive predictive value (PPV) was 79% (95% CI, 74%-84%). In subgroup analysis, true positive case numbers of PPF, IFA, CTD-ILD, sarcoidosis and EAA were 74/100 (74%), 95/100 (95%), 11/15 (73%), 27/32 (84%) and 6/22 (27%), respectively. CONCLUSIONS: This was the first ICD-9 coding validation for ILD in Hong Kong CDARS. Our study demonstrated that using ICD-9 algorithms 515, 516.3, 517.2, 517.8, 714.81 and 135 enhanced identifications of ILDs with PPV that was reliable to support utility of CDARS database for further clinical research on ILDs. The validity is particularly high with 516.3.

Continuous positive airway pressure improves blood pressure and serum cardiovascular biomarkers in obstructive sleep apnoea and hypertension.

BACKGROUND: The impact of treatment for obstructive sleep apnoea (OSA) on reduction of cardiovascular risk is unclear. This study aimed to examine the effect of continuous positive airway pressure (CPAP) on ambulatory blood pressure (BP) and subclinical myocardial injury in subjects with OSA and hypertension. METHODS: This was a parallel-group randomised controlled trial. Subjects with hypertension requiring at least three antihypertensive medications and moderate-to-severe OSA were enrolled. Eligible subjects were randomised (1:1) to receive either CPAP treatment or control (no CPAP) for 8 weeks. Changes in ambulatory BP and serum biomarkers were compared. Stratified analysis according to circadian BP pattern was performed. RESULTS: 92 subjects (75% male; mean±sd age 51±8 years and apnoea-hypopnoea index 40±8 events·h-1, taking an average of 3.4 (range 3-6) antihypertensive drugs) were randomised. The group on CPAP treatment, compared with the control group, demonstrated a significant reduction in 24-h systolic BP (-4.4 (95% CI -8.7- -0.1) mmHg; p=0.046), 24-h diastolic BP (-2.9 (95% CI -5.5- -0.2) mmHg; p=0.032), daytime systolic BP (-5.4 (95% CI -9.7- -1.0) mmHg; p=0.016) and daytime diastolic BP (-3.4 (95% CI -6.1- -0.8) mmHg; p=0.012). CPAP treatment was associated with significant BP lowering only in nondippers, but not in dippers. Serum troponin I (mean difference -1.74 (95% CI -2.97- -0.50) pg·mL-1; p=0.006) and brain natriuretic peptide (-9.1 (95% CI -17.6- -0.6) pg·mL-1; p=0.036) were significantly reduced in CPAP compared with the control group. CONCLUSIONS: In a cohort with OSA and multiple cardiovascular risk factors including difficult-to-control hypertension, short-term CPAP treatment improved ambulatory BP, and alleviated subclinical myocardial injury and strain.

Risk factors for Pseudomonas aeruginosa colonization in non-cystic fibrosis bronchiectasis and clinical implications.

BACKGROUND: Pseudomonas aeruginosa is one of the commonest bacteria colonizing the airway in patients with non-cystic fibrosis bronchiectasis. Pseudomonas aeruginosa colonization is associated with poor outcomes in patients with bronchiectasis, including rapid decline in lung function, exacerbation frequency and hospitalization. METHODS: A cross-sectional study in Queen Mary Hospital, Hong Kong that included 350 Chinese patients with non-cystic fibrosis bronchiectasis to investigate the risk factors for Pseudomonas aeruginosa colonization and clinical implications on disease outcomes. DISCUSSIONS: Pseudomonas aeruginosa colonization was more commonly found in patients with longer duration of bronchiectasis and those on proton pump inhibitors (PPIs) with adjusted ORs of 1.066 (95% CI = 1.036-1.096, p < 0.001) and 2.815 (95% CI = 1.307-6.064, p = 0.008) respectively. Patients with Pseudomonas aeruginosa colonization have more extensive lung involvement and higher risks of exacerbation requiring hospitalization with adjusted ORs of 2.445 (95% CI = 1.283-4.657, p = 0.007) and 2.745 (95% CI = 1.012-7.449, p = 0.047) respectively. Pseudomonas aeruginosa colonization is more common among patients with longer duration of bronchiectasis and those on PPI. Pseudomonas aeruginosa colonization is associated with more extensive lung involvement and higher risks of exacerbation requiring hospitalization.

Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations.

BACKGROUND: This study evaluated outcomes among patients with advanced/metastatic non-small-cell lung cancer (NSCLC) treated at Asian centers participating in the global named-patient-use (NPU) program for afatinib. METHODS: Patients had progressed after initial benefit with erlotinib or gefitinib, and/or had an EGFR or HER2 mutation, had no other treatment options, and were ineligible for afatinib trials. The recommended starting dose of afatinib was 50 mg/day. Dose modifications were allowed, and afatinib was continued as long as deemed beneficial. Response and survival information was provided voluntarily. Safety reporting was mandatory. RESULTS: 2242 patients (26% aged ≥ 70 years, 96% with adenocarcinoma) received afatinib at centers in 10 Asian countries. Most were heavily pre-treated, including prior treatment with erlotinib or gefitinib. Of 1281 patients tested, 1240 had EGFR mutations (common: 1034/1101; uncommon: 117/1101). There were no new safety signals, the most common adverse events being rash and diarrhea. Objective response rate (ORR) was 24% overall (n = 431 with data available), 27% for patients with common EGFR mutations (n = 230) and 28% for those with uncommon mutations (n = 32); median time to treatment failure (TTF) in these groups was 7.6 months (n = 1550), 6.4 months (n = 692) and 8.4 months (n = 83), respectively. In patients with EGFR exon 20 insertions (n = 23) and HER2 mutations (n = 12), median TTF exceeded 12 months. CONCLUSIONS: Patient outcomes in this study were similar to those reported in the analysis of the global NPU. Afatinib achieved clinical benefits in patients with refractory NSCLC. ORR and TTF were similar between patients with tumors harboring uncommon and common EGFR mutations.

Prevalence and Determinants of Sleep Apnea in Patients with Stroke: A Meta-Analysis.

OBJECTIVES: Recent meta-analyses have noted that ∼70% of transient ischemic attack (TIA)/stroke patients have sleep apnea. However, the heterogeneity between studies was high and did not appear to be accounted by the phase of stroke. We conducted an updated meta-analysis and aimed to determine whether the prevalence of sleep apnea amongst stroke patients differs by the subtype, etiology, severity and location of stroke and hence could account for some of the unexplained heterogeneity observed in previous studies. MATERIALS AND METHODS: We searched Medline, Embase, CINAHL and Cochrane Library (from their commencements to July 2020) for studies which reported the prevalence of sleep apnea by using polysomnography in TIA/stroke patients. We used random-effects model to calculate the pooled prevalence of sleep apnea and explored whether the prevalence differed by stroke characteristics. RESULTS: Seventy-five studies describing 8670 stroke patients were included in this meta-analysis. The overall prevalence of sleep apnea was numerically higher in patients with hemorrhagic vs. ischemic stroke [82.7% (64.4-92.7%) vs. 67.5% (63.2-71.5%), p=0.098], supratentorial vs. infratentorial stroke [64.4% (56.7-71.4%) vs. 56.5% (42.2-60.0%), p=0.171], and cardioembolic [74.3% (59.6-85.0%)] vs. other ischemic stroke subtypes [large artery atherosclerosis: 68.3% (52.5-80.7%), small vessel occlusion: 56.1% (38.2-72.6%), others/undetermined: 47.9% (31.6-64.6%), p=0.089]. The heterogeneity in sleep apnea prevalence was partially accounted by the subtype (1.9%), phase (5.0%) and location of stroke (14.0%) among reported studies. CONCLUSIONS: The prevalence of sleep apnea in the stroke population appears to differ by the subtype, location, etiology and phase of stroke.

Role of early definitive management for newly diagnosed malignant pleural effusion related to lung cancer.

BACKGROUND AND OBJECTIVE: The advent of effective anti-cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting. METHODS: Lung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re-intervention were identified with Cox proportional hazard analyses. RESULTS: Of the 509 records screened, 233 subjects were eligible. One hundred and twenty-seven subjects received oral targeted therapy as first-line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re-intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti-cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12-0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10-0.46, P < 0.001) were independently associated with longer time to MPE re-interventions. CONCLUSION: Early MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re-intervention, independent of anti-cancer therapies.

Efficacy of gefitinib at reduced dose in EGFR mutant non-small cell lung carcinoma.

As a first-generation epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib was approved by the US Food and Drug Administration for treatment of advanced non-small cell carcinoma with sensitizing EGFR mutations. Gefitinib is known to have adverse effects, which may necessitate dose reduction or even change to alternative preparation of epidermal growth factor receptor-tyrosine kinase inhibitor. There has been concern on dose reduction resulting in reduced dose gefitinib, especially on its efficacy. This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong that included 159 Chinese patients with advanced adenocarcinoma of lung that carried sensitizing EGFR mutations and had received gefitinib as first-line treatment. Patients who had reduced dose at 250 mg alternate day were compared with those who were able to maintain on standard dose of gefitinib at 250 mg daily. The primary end-point was progression-free survival. Among the 159 patients, 17 (10.7 %) of them were on reduced dose gefitinib, 14 among the 17 patients (82.4%) because of hepatotoxicity, and 3 (17.6%) because of cutaneous side effects. Patients on reduced dose and standard dose of gefitinib have comparable median progression-free survival. Hazard ratio was 1.121 (95% confidence interval = 0. 655-1.917, P-value = 0.678) for the reduced dose group and 3.385 for the standard dose group (95% confidence interval = 2.181-5.255) respectively (P-value < 0.001). Dose reduction in gefitinib to 250 mg alternate day in response to adverse effects was not associated with inferior outcome for patients on first-line gefitinib for advanced non-small cell carcinoma. Dose reduction is a feasible option for patients who have significant adverse effects with gefitinib.

CC16 levels correlate with cigarette smoke exposure in bronchial epithelial cells and with lung function decline in smokers.

BACKGROUND: Club cell protein-16 (CC16) expression has been associated with smoking-related lung function decline. The study hypothesis was that CC16 expression in both serum and bronchial epithelium is associated with lung function decline in smokers, and exposure to cigarette smoke will lead to reduction in CC16 expression in bronchial epithelial cells. METHODS: In a cohort of community-based male Chinese subjects recruited for lung function test in 2000, we reassessed their lung function ten years later and measured serum levels of CC16. CC16 expression was further assayed in bronchial epithelium from endobronchial biopsies taken from an independent cohort of subjects undergoing autofluorescence bronchoscopy, and tested for correlation between CC16 immunostaining intensity and lung function. In an in-vitro model, bronchial epithelial cells were exposed to cigarette smoke extract (CSE), and the expression levels of CC16 were measured in bronchial epithelial cells before and after exposure to CSE. RESULTS: There was a significant association between FEV1 decline and serum CC16 levels in smokers. Expression of CC16 in bronchial epithelium showed significant correlation with FEV1/FVC. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to CSE, followed by a subsequent rise in CC16 expression upon removal of CSE. CONCLUSIONS: Results of these clinical and laboratory investigations suggested that low serum CC16 was associated with smoking-related decline in lung function, demonstrated the first time in a Chinese cohort. The data also lend support to the putative role of CC16 in protection against smoking-related bronchial epithelial damage. (Abstract word count: 243) US CLINICAL TRIAL REGISTRY: NCT01185652 , first posted 20 August, 2010.

Nicotinic acetylcholine receptor expression in human airway correlates with lung function.

Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and ß3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.

The Impact of Obstructive Sleep Apnea and Tobacco Smoking on Endothelial Function.

BACKGROUND: Endothelial dysfunction has been recognized to occur in the context of obstructive sleep apnea (OSA) or tobacco smoking. However, the deleterious effect on vascular function with concurrence of both conditions is largely unknown. OBJECTIVE: To investigate whether the concurrence of OSA and smoking poses an additive detriment to endothelial dysfunction. METHODS: Chinese men without a history of chronic medical illness were invited to complete a questionnaire including smoking pack-year exposure, polysomnography and peripheral arterial tonometry (PAT) for endothelial function. Serum 8-isoprostane, advanced oxidation protein products (AOPP) and monocyte chemo-attractant protein-1 (MCP-1) were measured. RESULTS: 114 men were successfully enrolled. PAT ratio, adjusted for age and body mass index, correlated inversely with overall severity of OSA: apnea-hypopnea index (AHI), r = -0.160 (p = 0.092); oxygen desaturation index, r = -0.214 (p = 0.024); duration of oxygen saturation <90%, r = -0.219 (p = 0.020); and minimum oxygen saturation, r = 0.250 (p = 0.008). The PAT ratio decreased with increasing pack-year group (p = 0.018). It was lower with concurrent smoking history and moderate-severe OSA (AHI ≥15/h) compared to having one or neither factor (p = 0.011). Serum levels of 8-isoprostane and AOPP were positively related to severity of OSA, while MCP-1 correlated with smoking quantity. Multiple linear regression analyses showed that severity of intermittent hypoxia, MCP-1 and pack-year exposure were independent predictors of PAT ratio. CONCLUSION: While OSA, in particular intermittent hypoxemia, and tobacco smoking were independent risk factors, the concurrence of moderate-severe OSA and smoking was associated with the most severe impairment in endothelial function.

Inhalable paclitaxel nanoagglomerate dry powders for lung cancer chemotherapy: Design of experiments-guided development, characterization and in vitro evaluation.

Conventional intravenous chemotherapy for lung cancer frequently results in inefficient drug penetration into primary lung tumors and severe systemic toxicities. This study reports the development of inhalable paclitaxel (PTX) nanoagglomerate dry powders (PTX-NADP) for enhanced pulmonary delivery of PTX chemotherapy to lung tumors using full factorial Design of Experiments. PTX nanoparticles were fabricated by flash nanoprecipitation with the aid of N-polyvinylpyrrolidone (PVP) and curcumin (CUR) as stabilizer and co-stabilizer respectively, and subsequently agglomerated into inhalable dry powders via co-spray drying with methylcellulose. The optimized PTX-NADP formulation exhibited acceptable aqueous redispersibility (redispersibility index = 1.17 ± 0.02) into âˆ¼ 150 nm nanoparticles and superb in vitro aerosol performance [mass median aerodynamic diameter (MMAD) = 1.69 ± 0.05 µm and fine particle fraction (FPF) of 70.89 ± 1.72 %] when dispersed from a Breezhaler® at 90 L/min. Notably, adequate aerosolization (MMAD < 3.5 µm and FPF > 40 %) of the optimized formulation was maintained when dispersed at reduced inspiratory flow rates of 30 - 60 L/min. Redispersed PTX nanoparticles from PTX-NADP demonstrated enhanced in vitro antitumor efficacy and cellular uptake in A549 lung adenocarcinoma cells without compromising tolerability of BEAS-2B normal lung epithelial cells towards PTX chemotherapy. These findings highlight the potential of inhaled PTX-NADP therapy to improve therapeutic outcomes for lung cancer patients with varying levels of pulmonary function impairment.