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Herpes simplex virus type 1 (HSV1) pneumonia presents diagnostic challenges due to there being no gold-standard criteria currently. Specimens from bronchoalveolar lavage can increase specificity, and cytohistological examination can prove virus infection. Patients with high viral load have been reported with poor outcomes and benefited from antiviral agent. We describe an 80-year-old man with severe pneumonia who initially showed improvement without antiviral therapy, despite viral inclusion bodies on sputum cytology and positive HSV1 polymerase chain reaction from sputum, though subsequent clinical deterioration due to Pseudomonas aeruginosa infection necessitated intensive care. This case highlights the complexities of diagnosing and managing HSV1 pneumonia, emphasizing the importance of integrating clinical suspicion, radiological imaging, and laboratory tests for timely therapeutic decisions in critically ill patients. [ABSTRACT FROM AUTHOR]

Lung cancer has always been a burden to the society since its non-effective early detection and poor survival status. Different imaging modalities such as computed tomography scan have been practiced for lung cancer detection. This review focuses on the importance of sputum cytology for early lung cancer detection and biomarkers effective in sputum samples. Published articles were discussed in light of the potential of sputum cytology for lung cancer early detection and risk assessment across high-risk groups. Recent developments in sample processing techniques have documented a clear potential to improve or refine diagnosis beyond that achieved with conventional sputum cytology examination. The diagnostic potential of sputum cytology may be exploited better through the standardization and automation of sputum preparation and analysis for application in routine laboratory practices and clinical trials. The challenging aspects in sputum cytology as well as sputum-based molecular markers are to ensure appropriate standardization and validation of the processing techniques. [ABSTRACT FROM AUTHOR]

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most common malignancy in both gender. Early diagnosis is needed to reduce morbidity and mortality. There is a debate about the most accurate investigating modality for the diagnosis of lung cancer. Methods: It is a retrospective cohort analysis to determine whether an approach of combined contrast-enhanced computed tomography (CECT) thorax with bronchoscopy method has higher sensitivity and specificity than combined CECT thorax with sputum cytology method. Records of patients with lung cancer who had visited the hospital within the last 6 months were retrospectively analyzed for their diagnostic modality. SPSS version 19 software was used for statistical analysis of the data. CECT scan thorax, bronchoscopy, and sputum cytology for lung cancer patients were analyzed. The CECT thorax plus bronchoscopy method was compared with the CECT thorax plus sputum cytology method. Their sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in diagnosing lung cancer were analyzed. Results: Sixty-two patients were considered, including 62.9% males with a mean age of 55.5 years. In patients diagnosed with lung cancer, CECT thorax combined with bronchoscopy method was found to have a sensitivity of 96.67% than CECT thorax combined with sputum cytology method with a sensitivity of 90% and the difference in sensitivity between all individual approaches as well as the combined method was statistically significant with a P = 0.00001 and Chi-square value of 86.5909 owing to the low sensitivity of sputum cytology. CECT thorax combined with sputum cytology approach had a better specificity than CECT thorax combined with bronchoscopy. Conclusion: Combined CECT thorax with sputum cytology method has a better specificity in diagnosing lung cancer than combined CECT thorax with bronchoscopy method. [ABSTRACT FROM AUTHOR]

Background:Sputum cytology" is an example of exfoliative cytology, which is based on shedding of cells derived from the lining of an organ into a cavity from where they can be removed by non-invasive means. Aim:The study aimed to assess the value of PAP and AgNOR techniques in identification of bacterial infections and cytomorphological changes in sputum of Sudanese pango smokers. Methods: In this study 200 apparently healthy individuals volunteers were selected, of which 100 were pango smoker (cases) and 100 were non-pango users (control), Pap smear and AgNOR was used for the staining of sputum smears. All quality control measures were adopted during specimen collection and processing and diagnosis. Statistical Package for Social sciences (SPSS) software version 16 was used for data entry and analysis. Results: Findings demonstrated that the inflammation, indicated by presence of inflammatory cells was detected in 36/88among case group, most of them was chronic type, while only 5/100 had inflammation among non-smokers with significant relation, the p value is (0.000). The presence of infectious agent was illustrated among pango smokers most of them was bacterial and Actinomyces with significant relation the p value was (0.01). The nuclear atypia was reported among 5 out of 88 of heavy smoker's atypia. While no case of atypia was reported among non-smokers the p value is (0.217). Conclusions: Pango smoking is a major risk for occurrence of cellular changes that induce the prolifrative activity that increase the risk factor of lung cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between cough sensitivity and acute exacerbation in stable chronic obstructive pulmonary disease (COPD) patients., Methods: Stable COPD patients who visited our department from July 2022 to June 2023 were included. They were subjected to cough sensitivity test, spirometry, induced sputum cytology examination, questionnaire assessment such as cough symptom score, etc. They were followed up for 12 months, and were divided into the acute exacerbation (AE) group and the stable group according to whether acute exacerbation occurred during the follow-up period. We compared the differences in cough sensitivity, pulmonary function, and questionnaires between the two groups, analyzed the relationship between cough sensitivity and acute exacerbation, and screened the risk factors for AECOPD., Results: A total of 145 patients with stable COPD were included. AE group ( n  = 94) had lower FEV 1 /FVC (50.08 ± 11.11 versus 54.28 ± 11.58, p  = 0.03) and cough sensitivity lgC 5 [-0.01(0.90) versus 0.59(0.90), p  < 0.01] than those in the stable group ( n  = 51) patients, the daytime cough symptom score [2(2) versus 1(2), p  = 0.02] and VAS score [50(40) versus 30(50), p  < 0.01] were higher than stable group. Multivariate logistic regression analysis showed lgC 5 ( OR  = 0.34, 95% CI  = 0.16-0.71, p  < 0.01) was an independent risk factor for AECOPD. When lgC 5 was used to predict acute exacerbation in stable COPD patients, the AUC was 0.69, the sensitivity was 59.57%, and the specificity was 72.55%., Conclusion: Although causality is not necessarily demonstrated, baseline cough sensitivity lgC 5 in stable COPD patients is an independent risk factor for AECOPD, and it has some predictive value for future acute exacerbations.

Background: Severe eosinophilic asthma (SEA) may be the prodromal phase of eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease., Objective: To identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making., Methods: A total of 30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose, and throat, and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein, IL-5, IL-4, total-IgE, IgG 4 , and antineutrophil cytoplasmic antibody), sputum (eosinophils count, periostin, IL-8, and granulocyte-monocyte colony-stimulating factor [GM-CSF]), and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used., Results: Patients with SEA had poorer asthma control (P < .001) and a higher level of sputum eosinophils (P < .002), whereas patients with EGPA reported higher levels of blood eosinophils in the past. Sputum GM-CSF was the only biomarker significantly increased in patients with EGPA compared with those with SEA (P < .0001). Among patients with SEA, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GM-CSF (P < .0005), blood, and sputum eosinophils (P < .0006 and P < .011) than the other patients., Conclusion: Sputum GM-CSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in patients with SEA, suspected of having EGPA., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Specific inhalation challenge (SIC) tests are still the reference test for diagnosing sensitizer-induced occupational asthma (SIOA). The European Respiratory Society recommends the cessation of inhaled corticosteroids (ICS) 72 hours before SIC., Objective: To assess the effect of an ongoing ICS treatment during SIC on the maximum fall in forced expiratory volume in 1 second (FEV 1 ), the change in methacholine provocative concentration of methacholine inducing a 20% fall in FEV 1 (PC 20 ), and sputum eosinophil counts after exposure to the suspected agent., Methods: We performed a retrospective analysis using a database of cases referred to our center for suspected SIOA from 1999 to 2022. The results of the SIC were compared between subjects treated with ICS during SIC and steroid-naïve subjects., Results: Six hundred and seventy-one individuals underwent SIC in the laboratory. Three hundred and eighteen were treated with ICS, whereas 353 were steroid naïve. The proportion of subjects with a positive SIC was greater among ICS-treated subjects (39. 6%) compared with steroid-naïve subjects (27.5%, P < .001). A treatment with ICS did not influence the outcome of the SIC. There was no difference in the change in PC 20 or the percentage of sputum eosinophils after SIC between steroid-treated and steroid-naïve subjects., Conclusions: An ongoing ICS treatment during an SIC did not affect the occurrence of an asthmatic reaction, the change in airway responsiveness, or eosinophilic inflammation after exposure to the suspected agent in subjects who have been treated with ICS for a long period of time., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Myeloperoxidase (MPO) and human neutrophil lipocalin or neutrophil gelatinase-associated lipocalin (HNL/NGAL) are stored in neutrophil granulocytes and secreted upon activation of the cells. They have been proposed to reflect the degree of inflammation in the airways. However, their role as potential markers of disease severity in childhood asthma remains unknown. This study investigated the relationship between the expression of MPO and HNL/NGAL and childhood asthma., Methods: A total of 83 pediatric patients with asthma and 59 controls were enrolled. Using enzyme-linked immunosorbent assays, the human MPO and HNL/NGAL levels were measured in sputum supernatants. Assessments including spirometry, methacholine challenge test, and atopy test were conducted., Results: No difference in sputum neutrophil counts was observed between pediatric patients with asthma and controls. However, sputum MPO and HNL/NGAL levels were significantly higher in patients with asthma than in controls (p = 0.021 and p < 0.001, respectively), especially in patients with moderate-to-severe persistent asthma. In patients with asthma, sputum MPO and HNL/NGAL levels showed a positive correlation with sputum neutrophil counts (MPO, r = 0.433, p < 0.001; HNL/NGAL, r = 0.584, p < 0.001) and with each other (r = 0.628, p < 0.001). Moreover, sputum HNL/NGAL level demonstrated better ability to accurately reflect current pulmonary function, airway inflammation, and limitations than MPO level in this study., Conclusions: Sputum MPO and HNL/NGAL levels, which reflect neutrophil activation in airways, were increased in pediatric patients with asthma. Moreover, sputum MPO and HNL/NGAL may serve as appropriate assessment indicators of asthma severity in pediatric patients., (© 2024. The Author(s).)

Background: Although blood eosinophil count is recognized as a useful biomarker for the management of chronic obstructive pulmonary disease (COPD), the impact of eosinophils in COPD has not been fully elucidated. Here we aimed to investigate the relationships between the blood eosinophil count and various clinical parameters including lung structural changes., Methods: Ninety-three COPD patients without concomitant asthma were prospectively enrolled in this study. Blood eosinophil count, serum IgE level, serum periostin level, and chest computed tomography (CT) scans were evaluated. Eosinophilic COPD was defined as COPD with a blood eosinophil count ≧ 300/µL. We examined the correlation between the blood eosinophil count and structural changes graded by chest CT, focusing specifically on thin airway wall (WT thin ) and thick airway wall (WT thick ) groups. In a separate cohort, the number of eosinophils in the peripheral lungs of COPD patients with low attenuation area (LAA) on chest CT was assessed using lung resection specimens., Results: The mean blood eosinophil count was 212.1/µL, and 18 patients (19.3%) were categorized as having eosinophilic COPD. In the whole group analysis, the blood eosinophil count correlated only with blood white blood cells, blood basophils, C-reactive protein level, and sputum eosinophils. However, the blood eosinophil count positively correlated with the percentage of LAA and negatively correlated with the diffusing capacity for carbon monoxide in the WT thin group. Lung specimen data showed an increased number of eosinophils in the peripheral lungs of COPD patients with LAA on chest CT scans compared to normal controls., Conclusions: Some COPD patients without concomitant asthma showed a phenotype of high blood eosinophils. Alveolar damage may be related to eosinophilic inflammation in patients with COPD without asthma and thickening of the central airway wall., (© 2024. The Author(s).)

The detection of driver gene mutations has become essential for lung cancer; however, insufficient sample sizes make gene panel tests difficult to use. We previously reported that the lung cancer compact panel TM (LCCP) could detect EGFR and MET gene mutations with sputum cytology. To date, the detection of gene mutation using RNA from sputum samples is considered practically difficult. We report a case in which the EML4-ALK fusion gene was successfully detected from a sputum sample using the LCCP that was just released in Japan as a new next-generation sequencing lung cancer panel, CDx.

Background: Lung disease is viewed as perhaps the most far reaching and deadly malignancies all throughout the planet. The most seasoned and most crucial technique is based on sputum cytology. The last outskirts for getting sufficient material are fine needle yearning cytology (FNAC) of bronchial development. Aims and Objective: To relate the meaning of sputum cytology and fine needle goal cytology of bronchial tissue under CT rules for diagnosing cellular breakdown in the lungs. Materials and Methods: This potential observational investigation was completed by the division of medication in Chattogram Medical College Hospital, Chattogram, Bangladesh. Where data was collected from January 2019 to June 2020. A total of 50 patients with a suspected history, symptoms, and risk profile of having primary lung cancer, as demonstrated by chest radiography and CT scan, were chosen for the research population. Fifty patients with clinical and biochemical verification of suspected. All collected data were coding and input in SPSS-25 for further analysis. Both descriptive and inferential statistics were tested. Results: Among the 50 patients the vast majority of the patients were 51-60 years of age and the biggest number of the (94 %) patients were male. Sputum cytology is 8% touchy which isn’t steady with different examinations and CT guided FNAC is 94% sensitive. Conclusion: A definitive point of picture guided histological or cytological examination is to stay away from unnecessary thoracotomy and accomplish a particular determination with sensible exactness and least results. So, in this examination we found that sputum cytology is 8% delicate which isn’t steady with different investigations and CT guided FNAC is 94% touchy to last histological analysis of lung cancer. The discoveries recommended that CT guided FNAC discovered to be protected, feasible and viable.

Abstract Background Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype. Methods This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016–01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups. Results Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25–75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P

As more molecular-targeted drugs for advanced non-small cell lung cancer are brought to market, batch tests for the identification of gene mutations are needed at initial diagnosis. However, since current gene panel tests require a sufficient amount of tissue sample, there are many instances where panel tests cannot be performed. Therefore, we have developed a highly sensitive next generation sequencing (NGS) panel test to facilitate cytological specimens. Herein, we describe three cases positive for epidermal growth factor receptor (EGFR) exon 19 deletion, MET exon 14 skipping, and KRAS G12A using NGS analysis from sputum. In each case, genetic information was consistent with companion diagnostic analysis obtained from tissue samples collected under bronchoscopy. In cases of EGFR and MET mutations, the corresponding tyrosine kinase inhibitors were highly effective. This is the first report to demonstrate that a novel panel test could detect gene mutations in sputum samples in clinical practice and compare the gene allele ratio with the sample directly collected from the lesion. [ABSTRACT FROM AUTHOR]

Context: Differentiating NSCLC as either adeno or squamous type and identification of Epidermal Growth Factor Receptor (EGFR) mutations is clinically relevant for lung cancer patients for selecting treatment. Thyroid transcription factor-1 (TTF-1) and p63 were demonstrated as useful markers for histologic typing of lung cancer. Mutation and overexpression of EGFR has been reported in a subset of non-small cell lung cancers. If these markers can be validated for the differential diagnosis of adenocarcinoma in a sputum sample itself, it will be highly beneficial for lung cancer patients. Aims: To evaluate whether immunocytochemical expression of TTF-1, p63, and EGFR proteins in sputum samples can be used for differential diagnosis of lung adenocarcinoma by comparing with that of the corresponding tissue samples. Settings and Design: Ninety sputum samples and matched tissue samples were used for the study. Subjects and Methods: Monolayered smears and cell blocks of sputum and the corresponding tissue samples were immunostained with the standard ABC method. The expression patterns of these markers were analyzed statistically and compared with clinic-pathological parameters. Statistical Analysis Used: Chi-square test and paired t-test. Results: The p63 protein had a positive expression in 73.9% of SCC whereas TTF1 had positive expression in 75.8% of ADC. The EGFR expression was positive in 27 cases of adenocarcinoma, 21 cases of SCC and 19 cases of NSCLC. Conclusions: Immunocytochemistry of the aforementioned antibodies in sputum samples can be used as supplementary evidence for the subtyping of NSCLC.

Abstract Background Lung cancer has a very poor prognosis and high mortality. Positive sputum for malignant and/or atypical cells warrants the need for fibreoptic bronchoscopy. White light bronchoscopy (WLB) is usually unable to detect preinvasive lesions; therefore, autofluorescence bronchoscopy (AFB) was introduced as a gold standard for detecting such lesions. The aim of this work was to investigate the role of I-scan as a screening tool for cancer in smoker patients showing positive sputum cytology. Results New suspicious findings under I-scan occurred in 11 patients (36.7%). The overall sensitivity of WLB alone to diagnose malignancy is 23.3%, in contrast to an added sensitivity of 50% when I-scan was combined with white light (p value < 0.05). The specificity of I-scan could not be assessed in the absence of control cases (true negatives). No major complications or deaths occurred. Haemorrhage and bronchospasm were the commonest minor complications. Conclusions The addition of I-scan to the routine white light examination can increase the overall sensitivity of bronchoscopic screening in cases of sputum suspicious for malignancy if put in experienced hand. The suggested increase in procedure duration due to the combined use of I-scan and white light bronchoscopy is not associated with life-threatening complications.

BackgroundCoronavirus disease 2019 (COVID-19) pandemic continues to spread across the world. Specimens of blood, body fluids and excreta received in the department of pathology undoubtedly increased the risk of infection, especially in some hospitals that are short of professional protection capability. Here we provided a new simple way for the sputum cytology test during the COVID-19 pandemic.MethodsSputum samples from 30 patients with lung cancer were collected and divided into two groups, including the control group and the experimental group. Samples of the control group were processed in the biological safety cabinet, while the experimental group was put into the sealed specimen bag directly and pretreated with 75% medical alcohol. Then the cell morphology and tumor cell identification were analyzed by cell smears and liquid-based cell staining. The expression of cell antigens was determined by immunohistochemical staining.ResultOur result showed that both sputum samples in two groups exhibited complete cell structure and clear morphology according to the cell smear and liquid-based cell staining. In addition, the immunohistochemical result showed that cell antigens, including cytokeratin (CK), leukocyte common antigen (LCA), and thyroid transcription factor-1 (TTF1), were specifically expressed in the cell membrane, cytoplasm, and nucleus, respectively. The tumor cells were distributed diffusely, and cell antigens were located accurately after pretreatment with 75% medical alcohol and were consistent with that of the control group.ConclusionUsing 75% medical alcohol to pretreat sputum specimens has no obvious impact on cell morphology and antigens expression. Our study provided a new method for the sputum cytology test with no direct contact so as to protect medical staff against the virus during COVID-19 outbreak.

Background: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma., Methods: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed., Results: 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively., Conclusion: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction., Competing Interests: Conflict of interest: G.M. Gauvreau reports support for the present manuscript from AstraZeneca, grants from AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, and receipt of equipment, materials, drugs, medical writing, gifts or other services from AstraZeneca. R. Sehmi reports support for the present study from AstraZeneca. R. Leigh reports support for the present study from AstraZeneca, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca. D.W. Cockcroft reports support for the present manuscript from AstraZeneca, and grants from SHRF, Biohaven, AllerGen, University of Saskatchewan College of Medicine and CIHR. I. Mayers reports grants from AstraZeneca Canada and Boehringer Ingelheim, consultancy fees from Sanofi Canada and AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, and payment for expert testimony from Alberta Justice. L-P. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis and Sanofi-Regeneron, royalties or licences from UptoDate and Taylor & Francis, consultancy fees from AstraZeneca, Novartis, GlaxoSmithKline, Merck and Sanofi-Regeneron, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Novartis, Merck and Sanofi, and leadership role as Past-Chair of the Global Initiative for Asthma (GINA) Board of Directors, Past President of the Global Asthma Organisation (Interasma), Past Member of the Canadian Thoracic Society Respiratory Guidelines Committee and Past Laval University Chair on Knowledge Transfer, Prevention and Education in Respiratory and Cardiovascular Health. T. Ho reports grants from Fisher & Paykel, consultancy fees from Valeo and AstraZeneca, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and GlaxoSmithKline. I. Satia reports grants from Merck, GlaxoSmithKline and Bellus, consultancy fees from Merck, Genentech, Respiplus and GlaxoSmithKline/Bellus, and payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck, GlaxoSmithKline, AstraZeneca and Sanofi. P.D. Mitchell reports grants from Teva, consultancy fees from Pfizer and GlaxoSmithKline, and support for attending meetings from AstraZeneca. I.P. Magee reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GlaxoSmithKline. C. Bergeron reports support for the present study from AstraZeneca, grants from AstraZeneca, Sanofi and Regeneron, consultancy fees from ValeoPharma, Sanofi, AstraZeneca and GlaxoSmithKline, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, ValeoPharma, Sanofi and Grifols. M. Bhutani reports grants from CIHR, GlaxoSmithKline, AstraZeneca and Sanofi, consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Sanofi, Covis and Valeo, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Sanofi and Covis. V. Werkström was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. T. Durżyński was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. K. Shoemaker was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. R.K. Katial was an employee of AstraZeneca at the time of the study and reports personal fees from AstraZeneca. M. Jison was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. C. McCrae was an employee of AstraZeneca at the time of the study and reports stock or stock options in AstraZeneca. P.M. O'Byrne reports support for the present study from AstraZeneca, grants from AstraZeneca, Merck and Biohaven, consultancy fees from AstraZeneca, GlaxoSmithKline, Sage, Teva and Affibody, and payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Chiesi, GlaxoSmithKline and Covis. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.

Background: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations., Objective: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma., Methods: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on treatment arm and frequency of exacerbations., Results: Median sputum eosinophils were significantly lower among participants treated with mepolizumab compared with placebo (58% lower, 0.35% difference [95% CI 0.01, 0.74], P = .04). Clustering analysis identified 3 subpopulations of sputum eosinophils with varied expression of CD62L. CD62L int and CD62L hi eosinophils exhibited significantly elevated activation marker and eosinophil peroxidase expression, respectively. In mepolizumab-treated participants, CD62L int and CD62L hi eosinophils were more abundant in participants who experienced exacerbations than in those who did not (100% higher for CD62L int , 0.04% difference [95% CI 0.0, 0.13], P = .04; 93% higher for CD62L hi , 0.21% difference [95% CI 0.0, 0.77], P = .04)., Conclusions: Children with eosinophilic asthma treated with mepolizumab had significantly lower sputum eosinophils. However, CD62L int and CD62L hi eosinophils were significantly elevated in children on mepolizumab who had exacerbations, suggesting that eosinophil subpopulations exist that contribute to exacerbations despite anti-IL-5 treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary macrophages exhibit a dose-dependent pattern in phagocytizing particles. Following engulfment, these macrophages are subsequently excreted with sputum, rendering macrophages and particles visible and quantifiable under light microscopy. Notably, elemental carbon within the mammalian body originates exclusively from external contaminants. Consequently, the carbon content in airway macrophages (CCAM) serves as a valid exposure biomarker, accurately estimating individual exposure to carbon-containing particulate matter (PM). This article delineates a protocol involving sputum collection, preservation, processing, slide preparation, and staining, as well as macrophage photo acquisition and analysis. After removing the macrophage nuclei, the proportion of cytoplasm area occupied by carbon particles (PCOC) was calculated to quantify carbon content in each macrophage. The results indicate an elevation in CCAM levels after exposure to carbon-containing PM. In summary, this non-invasive, precise, reliable, and standardized method enables the direct measurement of carbon particles within target cells and is utilized for large-scale quantification of individual CCAM through induced sputum.

Background: Tailoring asthma interventions based on biomarkers could substantially impact the high cost associated with asthma morbidity. For policymakers, the main concern is the economic impact of adopting this technology, especially in developing countries. This study evaluates the budget impact of asthma management using sputum eosinophil counts in Colombia patients between 4 and 18 years of age., Methods: A budget impact analysis was performed to evaluate the potential financial impact of sputum eosinophil counts (EO). The study considered a 5-year time horizon and the Colombian National Health System perspective. The incremental budget impact was calculated by subtracting the cost of the new treatment, in which EO is reimbursed, from the cost of the conventional therapy without EO (management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma-related). Univariate one-way sensitivity analyses were performed., Results: In the base-case analysis, the 5-year costs associated with EO and no-EO were estimated to be US$ 532.865.915 and US$ 540.765.560, respectively, indicating savings for Colombian National Health equal to US$ 7.899.645, if EO is adopted for the routine management of patients with persistent asthma. This result was robust in univariate sensitivity one-way analysis., Conclusion: EO was cost-saving in guiding the treatment of patients between 4 and 18 years of age with persistent asthma. Decision-makers in our country can use this evidence to improve clinical practice guidelines, and it should be replicated to validate their results in other middle-income countries.

Background: Lung disease is viewed as perhaps the most far reaching and deadly malignancies all throughout the planet. The most seasoned and most crucial technique is based on sputum cytology. The last outskirts for getting sufficient material are fine needle yearning cytology (FNAC) of bronchial development. Aims and Objective: To relate the meaning of sputum cytology and fine needle goal cytology of bronchial tissue under CT rules for diagnosing cellular breakdown in the lungs. Materials and Methods: This potential observational investigation was completed by the division of medication in Chattogram Medical College Hospital, Chattogram, Bangladesh. Where data was collected from January 2019 to June 2020. A total of 50 patients with a suspected history, symptoms, and risk profile of having primary lung cancer, as demonstrated by chest radiography and CT scan, were chosen for the research population. Fifty patients with clinical and biochemical verification of suspected. All collected data were coding and input in SPSS-25 for further analysis. Both descriptive and inferential statistics were tested. Results: Among the 50 patients the vast majority of the patients were 51-60 years of age and the biggest number of the (94 %) patients were male. Sputum cytology is 8% touchy which isn't steady with different examinations and CT guided FNAC is 94% sensitive. Conclusion: A definitive point of picture guided histological or cytological examination is to stay away from unnecessary thoracotomy and accomplish a particular determination with sensible exactness and least results. So, in this examination we found that sputum cytology is 8% delicate which isn't steady with different investigations and CT guided FNAC is 94% touchy to last histological analysis of lung cancer. The discoveries recommended that CT guided FNAC discovered to be protected, feasible and viable. [ABSTRACT FROM AUTHOR]

Context: Differentiating NSCLC as either adeno or squamous type and identification of Epidermal Growth Factor Receptor (EGFR) mutations is clinically relevant for lung cancer patients for selecting treatment. Thyroid transcription factor-1 (TTF-1) and p63 were demonstrated as useful markers for histologic typing of lung cancer. Mutation and overexpression of EGFR has been reported in a subset of non-small cell lung cancers. If these markers can be validated for the differential diagnosis of adenocarcinoma in a sputum sample itself, it will be highly beneficial for lung cancer patients. Aims: To evaluate whether immunocytochemical expression of TTF-1, p63, and EGFR proteins in sputum samples can be used for differential diagnosis of lung adenocarcinoma by comparing with that of the corresponding tissue samples. Settings and Design: Ninety sputum samples and matched tissue samples were used for the study. Subjects and Methods: Monolayered smears and cell blocks of sputum and the corresponding tissue samples were immunostained with the standard ABC method. The expression patterns of these markers were analyzed statistically and compared with clinic-pathological parameters. Statistical Analysis Used: Chi-square test and paired t-test. Results: The p63 protein had a positive expression in 73.9% of SCC whereas TTF1 had positive expression in 75.8% of ADC. The EGFR expression was positive in 27 cases of adenocarcinoma, 21 cases of SCC and 19 cases of NSCLC. Conclusions: Immunocytochemistry of the aforementioned antibodies in sputum samples can be used as supplementary evidence for the subtyping of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Investigating the endotypes of the different asthma phenotypes would help disease monitoring, prognosis determination, and improving asthma management standardization. This study aimed to classify asthma into four endotypes according to the allergic and eosinophilic characteristics and explore the phenotypes (clinical characteristics, pulmonary functions, and fractional expired nitric oxide (FeNO)) of each endotype. Methods: This retrospective study included non-acute asthma patients treated at the First Hospital of Shanxi Medical University (05/2016–01/2018). The patients were classified into the eosinophilic allergic, eosinophilic non-allergic, non-eosinophilic allergic, and non-eosinophilic non-allergic asthma endotypes. Serum sIgE, lung function, FeNO, and induced sputum cytology were tested and compared among groups. Results: Of the 171 included patients, 22 had eosinophilic allergic asthma, 17 had eosinophilic non-allergic asthma, 66 had non-eosinophilic allergic asthma, and 66 had non-eosinophilic non-allergic asthma. Lung function measurements (FEV1%, FEF25%, FEF50%, FEF75%, and FEF25–75%) showed that airway dysfunction was worse in eosinophilic non-allergic asthma than in the other three endotypes (all P < 0.001). In allergic asthma patients, eosinophilic asthma had worse airway dysfunction than non-eosinophilic asthma (all P < 0.05). Similar results were found in non-allergic asthma (all P < 0.01). The FeNO levels in eosinophilic allergic asthma were higher than in eosinophilic non-allergic and non-eosinophilic non-allergic asthma (both P = 0.001). Conclusions: FeNO can objectively reflect eosinophilic airway inflammation in asthma. Endotypic classification of asthma patients regarding the allergic and eosinophilic characteristics is conducive to the effective management of patients with asthma. [ABSTRACT FROM AUTHOR]

Background: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment., Methods: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened., Results: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV 1 /FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV 1 , blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]., Conclusions: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV 1 /FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils., (© 2024. The Author(s).)

Introduction: The recently introduced World Health Organization (WHO) Reporting System for Lung Cytopathology presents 5 diagnostic categories with corresponding risk of malignancy (ROM) and management protocols. This study uses the system to categorize our institutional respiratory tract cytology specimens, evaluating ROM and diagnostic accuracy for each category., Materials and Methods: In a retrospective analysis (May 2020 to August 2021), the following respiratory cytology specimens were classified based on the WHO categories: bronchoalveolar lavage (BAL), bronchial wash/bronchial brushings (BB/BW), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), fine-needle aspiration cytology (FNAC), sputum, biopsy imprint (BI), and endotracheal wash. Exclusions comprised pleural effusions and EBUS-TBNA from mediastinal and hilar lymph nodes. Correlation of cytologic and histopathologic diagnoses was performed to assess ROM collectively and individually., Results: A total of 1518 respiratory samples (BAL [968], BW/BB [380], EBUS-TBNA [42], FNAC [32], sputum [80], BI [11] and endotracheal wash [5]) of 1410 patients were screened, of which 522 cases (34.3%) had histopathologic correlation. One hundred forty-one cases (9.3%) were Insufficient/Inadequate/Non-Diagnostic (ND), 1221 (80.4%) were Benign (B), 3 (0.2%) were Atypical (A), 32 (2.1%) were Suspicious for malignancy (SM) and 121 (8.0%) were Malignant (M). The estimated ROM for each category was 49.2% for ND, 13.3% for B, 66.6% for A, 81.5% for SM and 92.7% for M. FNAC and EBUS-TBNA exhibited the highest sensitivity (100%) compared with BW/BB (66.3%). Specificity ranged from 96.8% to 100% across the samples, while diagnostic accuracy varied from 58.8% to 100%., Conclusions: Application of the WHO reporting system enhances standardized terminology, aiding clinicians in informed decision-making and improving patient care through accurate risk assessment of malignancy., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Rationale: Bronchiectasis is an airway inflammatory disease that is frequently associated with chronic rhinosinusitis (CRS). An eosinophilic endotype of bronchiectasis has recently been described, but detailed testing to differentiate eosinophilic bronchiectasis from asthma has not been performed. Objectives: This prospective observational study aimed to test the hypotheses that bronchiectasis with CRS is enriched for the eosinophilic phenotype in comparison with bronchiectasis alone and that the eosinophilic bronchiectasis phenotype exists as a separate entity from bronchiectasis associated with asthma. Methods: People with idiopathic or postinfectious bronchiectasis were assessed for concomitant CRS. We excluded people with asthma or primary ciliary dyskinesia and smokers. We assessed sputum and blood cell counts, nasal NO and fractional excreted NO, methacholine reactivity, skin allergy testing and total and specific immunoglobulin (Ig) E, cytokines in the sputum and serum, and the microbiome in the sputum and nasopharynx. Results: A total of 22 people with CRS (BE + CRS) and 17 without CRS (BE - CRS) were included. Sex, age, Reiff score, and bronchiectasis severity were similar. Median sputum eosinophil percentages were 0% (IQR, 0-1.5%) in BE - CRS and 3% (1-12%) in BE + CRS ( P  = 0.012). Blood eosinophil counts were predictive of sputum eosinophilia (counts ⩾3%; area under the receiver operating characteristic curve, 0.68; 95% confidence interval, 0.50-0.85). Inclusion of CRS improved the prediction of sputum eosinophilia by blood eosinophil counts (area under the receiver operating characteristic curve, 0.79; 95% confidence interval, 0.65-0.94). Methacholine tests were negative in 85.7% of patients in the BE - CRS group and 85.2% of patients in the BE + CRS group ( P  > 0.99). Specific IgE and skin testing were similar between the groups, but total IgE levels were increased in people with increased sputum eosinophils. Microbiome analysis demonstrated distinct microbiota in nasopharyngeal and airway samples in the BE + CRS and BE - CRS groups, without significant differences between groups. However, interactome analysis revealed altered interactomes in individuals with high sputum eosinophil counts and CRS. Conclusions: Bronchiectasis with CRS is associated with an eosinophilic airway inflammation that is distinct from asthma.

Background In lung cancer, early diagnosis is the strongest predictor of survival and stage 1 is detected in only 15% of patients incidentally. To improve the outcomes, screening for cancer in the early stage in high-risk groups is a promising strategy. Aim The aim of this study was to assess the attitudes and knowledge of lung cancer screening practice in chest physicians. Patients and methods A self-administered questionnaire was distributed to a total of 75 chest physicians and the data were analysed. Results The survey illustrated that chest physicians believe that low-dose computed tomography (LDCT) is the most useful tool in screening for lung cancer in former and current smokers (31.3–62.5%) and it is a very effective screening test in reducing cancer mortality in never, former and current smokers (70%, 61.3 and 85%, respectively). Despite 90% of doctors having LDCT available in their geographic areas, 82.5% do not provide lung cancer screening for risk groups. Conclusion In Egypt, chest physicians believe that the use of LDCT screening for patients at high risk of lung cancer is an evidence-based recommendation by most programmes. Still most of them do not follow any screening program for risk groups. Education for doctors may increase the awareness, accuracy and efficacy of screening of high-risk patients.

Abstract Objectives Early diagnosis of lung cancer carries a good prognosis. The aim of the present study was early detection of lung cancer among heavy smokers using immunohistochemical staining and chest computed tomography (CT). Patients and methods This descriptive cross-sectional study comprised 80 heavy smokers with smoking index more than 40 pack-years. They were recruited from the Smoking Cessation Clinic, Mansoura University Hospital. All participants were subjected to (a) chest radiography followed by high-resolution chest CT, (b) sputum sample collection, and (c) fiberoptic bronchoscopy evaluation of bronchoalveolar lavage (BAL) and bronchial mucosal biopsies from suspicious areas. All pathological samples were stained with hematoxylin and eosin followed by immunostaining using antibodies for p53 and thyroid transcription factor-1 (TTF-1). Data were analyzed using statistical package for social sciences, version 16. Results The majority of heavy smokers were male, withamean age of 53.42±11.30 years. A solitary pulmonary nodule was detectedin1.3%of cases withchest radiographyandin5%with high-resolution CT. Hematoxylin and eosin staining of sputum, BAL, and mucosal biopsies was positive for premalignant changes in 35, 27, and 17.56%of cases, respectively. Sputum, BAL, and mucosal biopsies showed expression of p53 in 30, 37.8, and 35.1% of cases, respectively. Sputum, BAL, and mucosal biopsy showed expression of TTF-1 in 12.5, 10.8, and 14.9% of cases, respectively. Conclusion The immunohistochemical technique using p53 and TTF-1 is useful in the early detection of bronchial mucosal changes in heavy smokers. There is still need for a largescale study to highlight its validity and acceptability. Meanwhile, chest CT is beneficial for the detection of peripheral small lesions.

The lung is an extensively epithelialized organ, producing ample exfoliated material for sputum and bronchial cytology. In view of the updates in the World Health Organization classification of early (T1/≤ 3 cm) lung cancer with respect to adenocarcinomas with lepidic pattern, this study retrospectively reviews sputum and bronchial cytology paired with resection-confirmed lung cancers. A computerized search for all lung resection specimens of carcinomas over a 20-year period was performed. Cytologic diagnoses of corresponding sputum and bronchial cytology were classified into five-tiered categories (C1-insufficient/inadequate, C2-benign, C3-atypia, C4-suspicious and C5-malignant). Reports and slides of the resection specimen were reviewed for reclassification of T1 cancers. Totally 472 and 383 sputum and bronchial cytology specimens respectively were included. Sensitivity for T1 lesions on sputum cytology were 10.6 %, 2.1 % and 0.5 % at cutoffs of atypia/C3, suspicious/C4 and malignant/C5 categories, lower than bronchial cytology (35.1 %, 15.5 %, 8.1 %; p < 0.001). T1 lesions correlated with lower detection rates, whereas squamous cell carcinoma histology, larger size and bronchial invasion were associated with increased detection rates in sputum and bronchial cytology (p < 0.050). Detection rates for abrasive bronchial cytology (brushing) were overall higher (p = 0.018- < 0.001), but on subgroup comparison, non-abrasive (aspiration, lavage and washing) cytology demonstrated favorable trends (p = 0.063–0.088) in detecting T1 lesions. Adenocarcinomas with lepidic pattern had lower suspicious/C4 (p = 0.040) or above and malignant/C5 (p = 0.019), but not atypia/C3 or above (p = 0.517) rates. Most adenocarcinomas with lepidic pattern are only diagnosed as atypia/C3 on cytology. With its modest sensitivity, interpretation of negative and indeterminate cytology results mandates caution. • The detection rate of sputum cytology for lung cancer is low (< 10 %). • False negativity in bronchial cytology for early lung cancer is significant (65 %). • Bronchial invasion and squamous cell carcinoma are associated with positive cytology. • Lepidic adenocarcinomas cannot be reliably diagnosed by cytology. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related mortality in Japan and worldwide. Early detection of lung cancer is an important strategy for decreasing mortality. Advances in diagnostic imaging have made it possible to detect lung cancer at an early stage in medical practice. Conversely, screening of asymptomatic healthy populations is recommended only when the evidence shows the benefits of regular intervention. Due to a variety of evidence and racial differences, screening methods vary from country to country. This article focused on the perspective of lung cancer screening in Japan., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The study was carried out to examine whether chronic exposure to smoke during daily household cooking with biomass fuel (BMF) elicits changes in airway cytology and expressions of Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2]), Keap1 (Kelch-like erythroid-cell-derived protein with CNC homology [ECH]-associated protein 1), and NQO1 (NAD(P)H:quinone oxidoreductase 1) proteins in the airways. For this, 282 BMF-using women (median age 34 year) and 236 age-matched women who cooked with liquefied petroleum gas (LPG) were enrolled. Particulate matter with diameters of < 10 µm (PM10) and < 2.5 µm (PM2.5) were measured in indoor air with real-time laser photometer. Routine hematology, sputum cytology, Nrf2, Keap1, NQO1, and generation of reactive oxygen species (ROS) along with the levels of superoxide dismutase (SOD) and catalase were measured in both groups. PM10 and PM2.5 levels were significantly higher in BMF-using households compared to LPG. Compared with LPG users, BMF users had 32% more leukocytes in circulation and their sputa were 1.4-times more cellular with significant increase in absolute number of neutrophils, lymphocytes, eosinophils, and alveolar macrophages, suggesting airway inflammation. ROS generation was 1.5-times higher in blood neutrophils and 34% higher in sputum cells of BMF users while erythrocyte SOD was 31% lower and plasma catalase was relatively unchanged, suggesting oxidative stress. In BMF users, Keap1 expression was reduced, the percentage of AEC with nuclear expression of Nrf2 was two- to three-times more, and NQO1 level in sputum cell lysate was two-times higher than that of LPG users. In conclusion, cooking with BMF was associated with Nrf2 activation and elevated NQO1 protein level in the airways. The changes may be adaptive cellular response to counteract biomass smoke-elicited oxidative stress and inflammation-related tissue injury in the airways. [ABSTRACT FROM AUTHOR]

Abstract: Background: In mouse models of allergic asthma, exposure to different allergens can trigger distinct inflammatory subtypes in the airways. We investigated whether this observation extends to humans. Methods: We compared the frequency of sputum inflammatory subtypes between mild allergic asthma subjects (n = 129) exposed to different allergens in inhalation challenge tests. These tests were performed using a standardized protocol as part of clinical trials of experimental treatments for asthma, prior to drug randomization. Five allergen types were represented: the house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, ragweed, grass, and cat. Results: Of 118 individuals with a sputum sample collected before allergen challenge (baseline), 45 (38%) had paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic, and 11 (9%) mixed granulocytic sputum. Of note, most individuals with baseline paucigranulocytic sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum 7 hours after allergen challenge, highlighting the dynamic nature of sputum inflammatory subtype in asthma. Overall, there was no difference in the frequency of sputum inflammatory subtypes following challenge with different allergen types. Similar results were observed at 24 hours after allergen challenge. Conclusions: Unlike reported in mice, in humans the sputum inflammatory subtype observed after an allergen‐induced asthma exacerbation is unlikely to be influenced by the type of allergen used. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To establish the reference value of total and differential cell counts in induced sputum in healthy adults in Guangzhou, and to explore the relationship of age and gender with sputum cell counts. Methods: A total of 185 healthy, nonatopic, never‐smokers between 19 and 74 years old underwent induced sputum test with hypertonic saline (3%) inhalation. Sputum samples were collected for total and differential cell counts. Results: Qualified sputum samples were obtained from 153 subjects (mean age: 43 ± 17) with a success rate of 82.7% (153/185). The mean Standard Deviation (STDEV) and 2.5% to 97.5% percentile total cell counts were 2.1 × 106/g (1.0), (.7–4.5 × 106/g). The mean STDEV and 2.5% to 97.5% percentile differential cell counts were as follows: neutrophil 38.3% (17.7), (8.9%–72.9%); macrophage 58.9% (17.7), (24.7%–90.0%); eosinophils: median, .3%; interquartile range (IQR), 1.1%; and .0% to 95.0% percentile, .0% to 2.0%; and lymphocytes: median, 1.0%; IQR, 1.8%; and .0% to 95.0% percentile, .0% to 4.5%. There was positive correlation of age with the percentage of neutrophil and eosinophil (r = .659, r = .402; P < .001). The percentage of neutrophil, macrophage and eosinophil were significantly different among different age groups. The total cell counts and sputum cell counts were comparable between males and females. Conclusions: This study initially establishes reference value of induced sputum cell counts in healthy adults in Guangzhou, Southern China, and it verifies that neutrophilic and eosinophilic counts increase by age. [ABSTRACT FROM AUTHOR]