Advances in Respiratory Medicine

11 pages, 405 KiB

Open AccessReview

Pulmonary Toxicities of Immune Check Point Inhibitors in the Management of Cancer: Mini Review

by B Jayakrishnan, Mansour Al-Moundhri, Ikram Burney, Zamzam Al-Hashami and Khalid Al-Bimani

Adv. Respir. Med. 2022, 90(3), 219-229; https://doi.org/10.5603/ARM.84782 - 22 Jun 2022

Viewed by 2290

Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune response might lead to mild to severe immune-related adverse events (irAEs). Pulmonary toxicity, though often referred to as Immune checkpoint inhibitor–related pneumonitis (ICI-pneumonitis), [...] Read more.

Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of solid malignancies, leading in some cases to durable responses. However, an unchecked immune response might lead to mild to severe immune-related adverse events (irAEs). Pulmonary toxicity, though often referred to as Immune checkpoint inhibitor–related pneumonitis (ICI-pneumonitis), covers a broad and overlapping spectrum of pulmonary manifestations and has been described in <10% of patients receiving ICI either alone or in combination. However, the actual numbers in real-world populations are high, and are likely to increase as the therapeutic indications for ICIs continue to expand to include other malignancies. Drug withdrawal is the mainstay of treatment for ICI-pneumonitis. However, a good number of patients with higher grades of toxicity may need corticosteroids. Patients with refractory disease need additional immunosuppressive agents. In this brief review, we succinctly discuss the incidence, risk factors, mechanisms, clinical and radiologic manifestations, diagnosis and summarize the current management strategies of ICI-pneumonitis. Full article

8 pages, 705 KiB

Open AccessArticle

Correlation of the BMP-4 and BMP-7 Proteins Concentration and Expression in Response to a Specific and Non-Specific Trigger in Asthma

by Marcelina Koćwin, Michał Panek, Mateusz Jonakowski, Janusz Szemraj and Piotr Kuna

Adv. Respir. Med. 2022, 90(3), 211-218; https://doi.org/10.5603/ARM.87955 - 22 Jun 2022

Viewed by 1820

Abstract

Introduction: Asthma is characterized by persistent inflammation, airway hypersensitivity and remodelling. Bone Morphogenetic Proteins belong to the Transforming Growth Factor Superfamily and have a similar signalling transduction pathway and common co-mediating protein. However, the BMPs role in the remodelling remains unclear; they [...] Read more.

Introduction: Asthma is characterized by persistent inflammation, airway hypersensitivity and remodelling. Bone Morphogenetic Proteins belong to the Transforming Growth Factor Superfamily and have a similar signalling transduction pathway and common co-mediating protein. However, the BMPs role in the remodelling remains unclear; they appear to be involved in the airway inflammation and fibrogenesis process. Material and Methods: 60 patients with asthma and 48 healthy volunteers were recruited for the study. Blood samples were collected before, 1 h, 24 and 48 h after the allergen or the methacholine challenge test. Evaluation of BMP-4 and BMP-7 serum concentration and expression was performed using ELISA and real time PCR methods, respectively. Results: Statistically significant differences in BMP-7 concentration between healthy controls and asthmatics before the chal-lenge were noted. We found two statistically significant correlations: between the basal BMP-4 concentration and the FEV1(L) raw value and FEV1/FVC(%) index. We did not observe significant changes in the gene expression of BMP-4 and BMP-7 in different time points. Conclusions: Observed differences in BMP-7 concentration between asthmatic and healthy groups and correlations between BMP-4 concentration and some lung function test values may indicate the role of the BMPs in the etiopathogenesis of asthma. The unique characteristic of our study is the evaluation of BMPs serum levels, not in the bronchial epithelium. Full article

9 pages, 586 KiB

Open AccessArticle

Cardiopulmonary Exercise Testing versus Pulmonary Function Test in The Assessment of Respiratory Impairment in Chronic Obstructive Pulmonary Disease Patients

by Suzan Salama, Aliaë Abd-Rabou Mohamed-Hussein, Doaa M. Magdy and Aliaa Salama

Adv. Respir. Med. 2022, 90(3), 202-210; https://doi.org/10.5603/ARM.84410 - 22 Jun 2022

Cited by 5 | Viewed by 2240

Abstract

Introduction: Cardiopulmonary exercise testing (CPET) is a non-invasive method for the determination of disability and comprehensive evaluation of exercise responses involving the cardiovascular, pulmonary and musculoskeletal systems. Material and Methods: To assess exercise performance measured by CPET in different chronic obstructive [...] Read more.

Introduction: Cardiopulmonary exercise testing (CPET) is a non-invasive method for the determination of disability and comprehensive evaluation of exercise responses involving the cardiovascular, pulmonary and musculoskeletal systems. Material and Methods: To assess exercise performance measured by CPET in different chronic obstructive pulmonary disease (COPD) stages and to compare between pulmonary function test (PFT) and CPET in assessing the degree of respiratory impairment. Sixty patients diagnosed with COPD were enrolled in the study. Modified Medical Research Council scale (mMRC) and COPD assessment test (CAT) to evaluate dyspnea symptom. PFT and CPET were performed. Results: There was a significant decrease in peak VO₂ and anaerobic threshold in patients with stages III, IV (p < 0.001), while COPD stage I, II had significantly higher minute ventilation, tidal volume and oxygen pulse (p < 0.001). 76.67% of patients were similarly classified by CPET and PFT, while 23.33% were found to be less impaired according to CPET when compared to PFT. A significant correlation between both VE/VO2 (r = 0.31, 95% CI 0.19–0.92, p < 0.001) and VE/VCO2 (r = 0.69, 95% CI 0.86–1.08, P < 0.001) with FEV1. Whereas, an inverse correlation were found between both VE/VCO 2 (r = –0.34, 95% CI –0.77 –1.11, p < 0.001) and VE/VO₂ (r = –0.55, 95% CI –0.88 to –0.15, p < 0.001), with the degree of air trapping as estimated by RV/TLC ratio. No significant correlation between neither CAT nor MRC and exercise testing parameters. Conclusion: CPET is an extremely valuable method for the determination of functional capacity and exercise intolerance in COPD rather than PFT. CPET is considered a gold-standard tool for better evaluation of respiratory impairment in COPD. Full article

9 pages, 1007 KiB

Open AccessArticle

Clinical Characteristics, Treatment Outcomes and Factors Associated with Severe Illness in 813 COVID-19 Patients Admitted in A Tertiary Care Hospital of Eastern India

by Deependra Kumar Rai, Ameet H, Pallavi Lohani, Sanjay Pandey and Harsh Vardhan

Adv. Respir. Med. 2022, 90(3), 193-201; https://doi.org/10.5603/ARM.83259 - 22 Jun 2022

Cited by 1 | Viewed by 1841

Abstract

Introduction: This retrospective observational study has been designed to identify clinical characteristics, treatment outcomes and factors associated with severe illness in 813 COVID-19 patients hospitalised in an Indian tertiary care hospital. Material and Methods: This was a retrospective analysis of patient [...] Read more.

Introduction: This retrospective observational study has been designed to identify clinical characteristics, treatment outcomes and factors associated with severe illness in 813 COVID-19 patients hospitalised in an Indian tertiary care hospital. Material and Methods: This was a retrospective analysis of patient admitted between 1 July to 15 August 2020 with COVID-19 infections. Logistic regression was performed to explore the association of clinical characteristics and laboratory parameters with the risk of severe disease and mortality. The statistical significance level was set at 0.05 (two-tailed). Results: Out of 813 study patients, 630 (77.50%) patients were categorised with mild to moderate while 183 (22.50%) patients as severe Covid infection. Mortality was significantly higher in severe Covid patients as compared to mild moderate cases (66.21% vs. 10.31%. p < 0.0001. Patients with severe infection were significantly more likely to have diabetes hypertension, chronic kidney disease (CKD) and had significantly higher Neutrophil count, serum creatinine, C-reactive protein (CRP), ferritin, D-Dimer and decreased haemoglobin, lymphocyte and serum calcium than patients with mild-moderate infection. In Multivariate analy-sis, age more than 60 years [AOR: 2.114, 95% CI (1.05–4.254), 0.036], NLR more than 3.3 [AOR: 1.082, 95% CI (1.030–1.137), 0.002] and D-Dimer >1 μg/mL [AOR: 2.999 (1.464–6.146), 0.003] were found significantly associated with severe disease (p < 0.05). Factors associated with mortality were age more than 60 years, presence of breathlessness, severe disease or presence of chronic kidney disease. Conclusions: Factors like elderly age (age > 60 years), elevated NRL, CRP, D-Dimer and serum ferritin were associated with sig-nificantly higher risk to develop severe COVID-19 infections. Elderly, and patients with CKD were associated with worse outcome. Full article

3 pages, 790 KiB

Open AccessLetter

Ad Hoc Afatinib in an Eldery Lung Cancer Patient with EGFR Exon 19 Deletion L747-A750>P

by Annalisa Guida, Valentina Tassi, Francesco Facchinetti, Giovanni Marchetti, Cecilia Caprera, Mark Ragusa, Marcello Tiseo and Sergio Bracarda

Adv. Respir. Med. 2022, 90(3), 234-235; https://doi.org/10.5603/ARM.a2022.0034 - 17 May 2022

Viewed by 1690

Abstract

Approximately 10–20% of patients with non–small-cell lung cancer (NSCLC) harbor an epidermal growth factor receptor (EGFR) [...] Full article

7 pages, 572 KiB

Open AccessArticle

Endosonography and Endosonography Guided Needle Aspiration for Left Adrenal Gland Assessment in Lung Cancer Patients―10 Years’ Experience

by Stanisław Orzechowski, Maciej Gnass, Jacek Wojtacha, Anna Filarecka, Damian Czyżewski, Juliusz Pankowski, Adam Ćmiel and Artur Szlubowski

Adv. Respir. Med. 2022, 90(3), 157-163; https://doi.org/10.5603/ARM.a2022.0033 - 13 May 2022

Cited by 3 | Viewed by 1746

Abstract

Introduction: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis. Material [...] Read more.

Introduction: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis. Material and Methods: A retrospective study of consecutive LCP was conducted in two pulmonology centers between January 2010 and December 2019. Records of complete endosonographic staging with use of single ultrasound bronchoscope or two scopes were overviewed. The analysis included cases of enlarged LAG (body size or limbs > 10 mm) examined and sampled by EUS-b-FNA or EUS-FNA. Results: 142 of 2596 LCP staged by complete endosonography (M: 88, F: 54 mean age 64.7) had enlarged LAG, which were biopsied by conventional EUS-FNA (52) and/or by EUS-b-FNA (90). Strong correlation with gland diameter (p < 0.001) was observed. The incidence of LAG metastases in analyzed group was 52.1% (74/142) and regarding histology: SCLC 76.9% (10/13), adenocarcinoma 66.7% (44/66), NSCLC 56.3% (9/16) and SCC 17.5% (7/40). A specificity and PPV for both methods were 100%. A sensitivity, accuracy and NPV for EUS-FNA were 91.7%, 96.2%, 93.3% and for EUS-b-FNA 88%, 93.3% and 87%, respectively and no significant differences for both methods were noted (p = 0.62, 0.44, 0.35). No severe complications afterall biopsies were observed. A six months clinical follow up included all negative LCP with enlarged LAG. Conclusions: After our study EUS-b-FNA seems to be a reasonable method of choice for LAG assesssment in LCP. Full article

7 pages, 1049 KiB

Open AccessArticle

Gait Speed Predictors and Gait-Speed Cut-Off Score to Discriminate Asthma Control Status and Physical Activity in Patients with Asthma

by Ismail Ozsoy, Muhammed Ihsan Kodak, Nermin Zerman, Caner Karartı, Gulsah Ozsoy and Arzu Erturk

Adv. Respir. Med. 2022, 90(3), 164-170; https://doi.org/10.5603/ARM.a2022.0031 - 14 Apr 2022

Cited by 3 | Viewed by 1833

Abstract

Introduction: As a “vital sign” of health and functional capacity, gait speed is commonly used. However, there is insufficient evidence for possible determinants of gait speed in patients with asthma. The primary objective of the present study was to determine predictors of [...] Read more.

Introduction: As a “vital sign” of health and functional capacity, gait speed is commonly used. However, there is insufficient evidence for possible determinants of gait speed in patients with asthma. The primary objective of the present study was to determine predictors of gait speed in patients with asthma. The second objective was to determine the cut-off point for the 4-min Gait Speed (4MGS) to better discriminate asthma control status and physical activity in asthma. Material and Methods: Fifty-seven patients with asthma were included in this cross-sectional study. Demographic and clinic characteristics, pulmonary function, asthma control status (ACT, Asthma Control Test), dyspnea, gait speed (4MGS), physical activity [International Physical Activity Questionnaire-Short Form (IPAQ-SF)] and activities of daily living were evaluated. Stepwise multiple linear regression analysis was used to investigate the possible predictors of gait speed. Receiver operating characteristic (ROC) curve analysis was used to determine whether usual gait speed had a discriminative value. Results: The stepwise multiple regression analysis revealed that the ACT score and the IPAQ-SF score were significant and independent predictors of the 4MGS in patients with asthma explaining 40% of the variance in 4MGS (p < 0.001). The ROC curve showed a cut-off point of 1.06 m/s for the 4MGS for poorly controlled asthma and physical inactivity (p < 0.05). Conclusions: Our findings indicate that asthma control status and physical activity can be independent predictors of gait speed in patients with asthma. In addition, gait speed may be discriminative to determine poorly controlled asthma and physical inactivity in patients with asthma. Full article

4 pages, 227 KiB

Open AccessCommunication

Should a Prescription Database Be Used to Search Uncontrolled Severe Asthmatics?

by Bruno Sposato, Elisa Petrucci, Fabio Lena, Leonardo Gianluca Lacerenza, Michele Bindi, Andrea Montagnani, Antonio Perrella and Marco Scalese

Adv. Respir. Med. 2022, 90(3), 230-233; https://doi.org/10.5603/ARM.a2022.0019 - 31 Jan 2022

Viewed by 1593

Abstract

Introduction: Many uncontrolled severe asthmatics are not on biologic therapy. We hypothesized that using a prescription database could help us identify them. Material and Methods: 3309 patients who received at least one Montelukast prescription in 2019 were extracted from our prescription [...] Read more.

Introduction: Many uncontrolled severe asthmatics are not on biologic therapy. We hypothesized that using a prescription database could help us identify them. Material and Methods: 3309 patients who received at least one Montelukast prescription in 2019 were extracted from our prescription database. Number of packages/year, types and dosages of ICS, LABA, ICS/LABA, LAMA and monoclonal antibodies were considered for each patient. In our analysis, for subjects that took > 7 packages of ICS/LABA + LTRA +/– LAMA (high adherent) the number of oral corticosteroids (OC) packets prescribed for each of them was also looked upon. Results: Patients that took ICS/LABA or ICS/LABA + LAMA continuously with high ICS doses were 188 (25.6%) and 117 (39.3%) respectively (total: 305 — 29.5%). Among them, 58 (30.9%) and 53 (45.3%) (total: 111 — 36.4%) were prescribed more than 2 OC packages. Whereas, 21 (11.2%) and 24 (20.5%) patients (total: 45 — 14.75%) received at least 4 OC package prescriptions. Conclusion: Approximately 36% of patients in continuous step-4/5 of GINA Guideliness treatment may have severe uncontrolled asthma (overusing OC) which needed biologic treatment. In our opinion, a prescription archiving database may be a tool that can help us identify such uncontrolled asthma patients. Full article

12 pages, 2006 KiB

Open AccessArticle

Cardiotoxicity of Azithromycin in COVID-19: An Overall Proportion Meta-Analysis

by Ioannis Farmakis, Ioanna Minopoulou, George Giannakoulas and Afroditi Boutou

Adv. Respir. Med. 2022, 90(3), 171-182; https://doi.org/10.5603/ARM.a2022.0022 - 31 Jan 2022

Cited by 3 | Viewed by 2015

Abstract

Introduction: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. Material and Methods: We searched PubMed, the Cochrane Library and Web of [...] Read more.

Introduction: To explore the incidence of pro-arrhythmic effects such as corrected QT interval (QTc) prolongation, arrhythmic events and myocardial injury of azithromycin as administered for the treatment of COVID-19. Material and Methods: We searched PubMed, the Cochrane Library and Web of Science databases from inception to 18 January 2021, as well as the medRχiv preprint database from 1 August 2020 to 18 January 2021, for studies exploring the cardiotoxicity effects of azithromycin, with or without concomitant use of hydroxychloroquine, in the context of COVID-19. We performed a random effects single-arm meta-analysis of studies to calculate pooled proportion estimates for pro-arrhythmic effects. Meta-regression analyses were conducted to explain between-study heterogeneity. Results: Thirty-four studies with a total of 3088 patients were included. Among 12 studies, the incidence of >60 ms QTc prolongation from baseline was 13% (95% CI 9%–18%, I² = 73%), whereas, among 28 studies, the incidence of QTc ≥ 500 ms at follow-up was 8% (95% CI 6%–11%, I² = 78%). Still, the discontinuation rate due to QTc prolongation was only 3% (95% CI 2%–5%, I² = 55%). The absolute risk of Torsade de pointes and ventricular tachycardia was 0.2% and 0.8%, respectively. Increased age, male sex, presence of hypertension or diabetes mellitus, use of QTc prolonging medication, prolonged baseline QTc interval and indicators of disease severity such as death explained between-study heterogeneity. Conclusions: Azithromycin, with or without hydroxychloroquine, leads to a significant risk for critical QTc prolongation in patients with COVID-19. Due to its cardiotoxicity effects and its unproven efficacy in Covid19, azithromycin use should be limited to cases of bacterial co-infection. Full article

10 pages, 619 KiB

Open AccessArticle

The Levels and Correlations of FeNO, Blood Eosinophils and Lung Function in Well-Controlled Asthma

by Narongwit Nakwan, Thidarat Ruklerd, Thitima Perkleang and Pattarawadee Taptawee

Adv. Respir. Med. 2022, 90(3), 183-192; https://doi.org/10.5603/ARM.a2022.0015 - 28 Jan 2022

Cited by 4 | Viewed by 1808

Abstract

Introduction: Whether biomarkers (i.e., fractional exhaled nitric oxide (FeNO) and blood eosinophils) or lung function are additional ultimate outcomes in asthma treatment among patients with clinical remission has been the subject of previous research, the study of the correlations between FeNO, blood [...] Read more.

Introduction: Whether biomarkers (i.e., fractional exhaled nitric oxide (FeNO) and blood eosinophils) or lung function are additional ultimate outcomes in asthma treatment among patients with clinical remission has been the subject of previous research, the study of the correlations between FeNO, blood eosinophils and lung function among well-controlled asthmatic patients is less clear. To investigate the clinical application of the correlation between FeNO, blood eosinophils and lung function parameters in well-controlled asthmatic patients. Material And Methods: This was a prospective cross-sectional study. We measured FeNO, blood eosinophil and lung function in 84 asthmatic patients with clinical remission who were assessed by asthma control questionnaires. The correlation coefficient was used to ascertain among those parameters. The diagnostic accuracy of blood eosinophil to identify low FeNO (<25 ppb) was calculated using the area under the receiver operating characteristics (AUROC). Results: Of 84 patients analyzed, the median ACT was 25 and the median ACQ-7 was 0.43. The median duration of being well-controlled asthma was 14.5 months. The median FeNo was 23 ppb and the median blood eosinophils was 375 cell/mm³. A significant positive correlation was found between FeNo and blood eosinophil (r = 0.310, p = 0.004). No correlation was detected between either FeNO or blood eosinophil and all lung function parameters. The AUROC results for blood eosinophils was 64.4% (p = 0.024) to detect FeNO < 25 ppb at a cutoff point of 295 cell/mm³ (sens tivity = 83.5%, specificity = 50%). Conclusion: Measuring FeNO and blood eosinophils in patients with a clinical remission of asthma may determine which of those patients have achieved complete remission. As the level of blood eosinophils has a significant correlation with FeNO, it may easily be a feasible biomarker to evaluate inactive airway inflammation before stepping down asthma treatment. Full article

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Adv. Respir. Med., Volume 90, Issue 3 (June 2022) – 10 articles

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