Annals of Thoracic Medicine Official publication of the Saudi Thoracic Society, affiliated to King Saud University
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   2021| April-June  | Volume 16 | Issue 2  
    Online since April 17, 2021

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Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials
Ahmed Abu-Zaid, Aseel Khalid Aljaili, Amnah Althaqib, Fatima Adem, Doaa Ali Alhalal, Amena Faiq Almubarak, Saud Musaab Aldughaither, Sarah Ali Alghabban, Ghaidaa Alfaraj, Ahmed Taher Masoud, Nujud Abdullah Alsuhaibani
April-June 2021, 16(2):127-140
AIM: We conducted this systematic review and meta-analysis to investigate the efficacy and safety of gefapixant, a novel P2X3 receptor antagonist, in patients with chronic cough. METHODS: We searched four databases for randomized controlled trials (RCTs). We assessed the cough frequency, severity, total Leicester cough questionnaire (LCQ) score, and adverse events. We analyzed the data using Open Meta-Analyst and Review Manager Software. RESULTS: We included four unique studies (comprising five stand-alone RCTs) with 439 patients. Compared to placebo, gefapixant had positive anti-tussive effects by improving awake cough frequency (mean difference [MD] = −5.27, 95% confidence interval [CI] [−6.12, −4.42], P < 0.00001), night cough frequency (MD = −3.71, 95% CI [−6.57, −0.85], P = 0. 01), 24 h cough frequency (MD = −4.18, 95% CI [−5.01, −3.36], P < 0.00001), cough severity using the Visual Analog Scale (MD = −13.36, 95% CI [−17.80, −8.92], P < 0.00001), cough severity diary (MD = −0.88, 95% CI [−1.25, −0.51], P < 0.00001), and total LCQ score (MD = 2.00, 95% CI [1.15, 2.86], P = 0. 00001). Meta-regression analyses showed a positive correlation between the gefapixant dose and the incidence of any adverse event (relative risk [RR] = 0.239, 95% CI [0.093, 1.839], P = 0.001) and incidence of adverse event related to treatment (RR = 0.520, 95% CI [0.117, 0.922], P = 0.011). CONCLUSIONS: In patient with chronic cough, gefapixant exhibits favorable anti-tussive outcomes by improving the cough frequency, severity, and quality of life. While gefapixant is largely tolerable, its side effects (notably taste alteration) are dose dependent.
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Prognostic utility of inflammation-based biomarkers, neutrophil–lymphocyte ratio and change in neutrophil–lymphocyte ratio, in surgically resected lung cancers
Daniel Thompson, Luke A Perry, Jesse Renouf, Domagoj Vodanovich, Adele Hwee Hong Lee, Jahan Dimiri, Gavin Wright
April-June 2021, 16(2):148-155
BACKGROUND/OBJECTIVE: Given the poor overall survival (OR) and progression-free survival (PFS) rates for lung cancers managed with surgical resection, there is a need to identify the prognostic markers that would improve the risk stratification of patients with operable lung cancer to inform treatment decisions. We investigate the prognostic utility of two established inflammation-based scores, the neutrophil–lymphocyte ratio (NLR) and the change in neutrophil–lymphocyte ratio (ΔNLR), throughout the operative period in a prospective cohort of patients with lung cancer who underwent surgical resection. METHODS: Demographic, clinical, and treatment details for 345 patients with lung cancer who underwent surgical resection between 2000 and 2019 at multiple centers across Melbourne, Victoria (Australia), were prospectively collected. Preoperative NLR and ΔNLR were calculated after which Cox univariate and multivariate analyses were conducted for OS and PFS against the known prognostic factors. RESULTS: Both univariate and multivariate analyses showed that preoperative NLR >4.54, as well as day 1 and day 2 postoperative NLR (P < 0.01), was associated with increased risk for postoperative mortality (hazard ratio 1.8; P < 0.01) and PFS (P < 0.05), whereas ΔNLR was not a significant predictor of OS or PFS. CONCLUSION: Elevated NLR among patients with lung cancer who underwent surgical resection was prognostic for poor OS and PFS, whereas ΔNLR was not found to be prognostic for either OS or PFS. Further research may yet reveal a prognostic value for ΔNLR when compared across a greater time period.
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The risk of coronavirus to healthcare providers during aerosol-generating procedures: A systematic review and meta-analysis
Sharafaldeen A Bin Nafisah, Bandr Y Mzahim, Bakhitah S Aleid, Shahad A Sheerah, Daliah Q Almatrafi, Gregory R Ciottone, Khalid H AlAnazi, Anas A Khan
April-June 2021, 16(2):165-171
CONTEXT: Several medical procedures are thought to increase the risk of transmission of infectious agents to health-care providers (HCPs) through an aerosol-generating mechanism. AIMS: Given the significant influenza and coronavirus pandemics that have occurred in the 20th and 21st century, including the current severe acute respiratory syndrome coronavirus 2 global pandemic, the objective of this analysis is to assess the occurrence of disease transmission to HCPs from the performance aerosol-generating procedures (AGPs). SETTINGS AND DESIGN: This was a systematic review and meta-analysis SUBJECTS AND METHODS: We performed a systematic meta-analysis looking at the odds ratio (OR) of AGP, causing infection among HCPs. We searched the following databases: MEDLINE (PubMed), ProQuest, Cochrane databases, and the Gray literature ( and World Health Organization International Clinical Trials Registry Platform). In addition, we conducted nondatabase search activities. The search terms used were “MERS-CoV,” “COVID,” and “SARS” combined with “provider” or “healthcare provider.” STATISTICAL ANALYSIS USED: RevMan meta-analysis was used for statistical analysis. RESULTS: Following the search, we reviewed 880 studies, of which six studies were eligible. The estimated odd ratio utilizing a control group of HCPs who were exposed to AGP but did not develop the infection was 1.85 (95% confidence interval [CI]: 1.33, 2.57). The OR remained the same when we added another control group who, despite not being exposed to AGP, had developed the infection. The OR remained 1.85 (95% CI: 1.33, 2.55). However, there is an increase in the OR to 1.89 (95% CI: 1.38, 2.59) when we added HCPs who did not use adequate personal protective equipment (PPE) during the procedures to the total estimates. CONCLUSIONS: The performance of AGP with inadequate PPE can result in an increased risk of disease transmission to HCWs.
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Acute exacerbation in interstitial lung disease
Esam H Alhamad, Joseph G Cal, Nuha N Alrajhi, Ahmad A AlBoukai
April-June 2021, 16(2):178-187
BACKGROUND: Information regarding acute exacerbation (AE) in patients with interstitial lung disease (ILD) is limited. OBJECTIVES: The objective of the study was to elucidate the clinical features and outcome of AE among ILD patients. METHODS: We retrospectively analyzed the data of 667 consecutive ILD (nonidiopathic pulmonary fibrosis [IPF] ILD, n = 463; IPF, n = 204) patients. ILD patients meeting the 2016 definition of AE-IPF were identified. Information analyzed included pulmonary function tests, 6-min walk tests, and right heart catheterization data, among others. Cox regression models were used to identify independent predictors of survival. RESULTS: AE was identified in non-IPF ILD (n = 113) and IPF (n = 74). Compared with AE-IPF patients, non-IPF ILD patients with AE were of younger age, predominantly women, and primarily nonsmokers (all, P < 0.0001). The estimated survival probabilities at 1, 3, and 5 years were 88%, 75%, and 70%, respectively, in the ILD without AE group; 80%, 57%, and 50%, respectively, in the non-IPF ILD with AE group; and 53%, 38%, and 28%, respectively, in the AE-IPF group (P < 0.0001 by log-rank analysis). Age, body mass index, IPF diagnosis, AE, diffusion capacity of the lung for carbon monoxide <35% predicted, 6-min walk distance <300 meters, and cardiac index were independent predictors of survival in the ILD cohort. CONCLUSIONS: Non-IPF ILD patients with AE have distinct clinical features compared to AE-IPF patients. Importantly, AE is one of many independent risk factors associated with worsened outcomes regardless of the underlying ILD type.
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Application of aerosol therapy in respiratory diseases in children: A Saudi expert consensus
Adel S Alharbi, Abdullah A Yousef, Saleh A Alharbi, Abdullah Al-Shamrani, Mansour M Alqwaiee, Mohammed Almeziny, Yazan S Said, Saleh Ali Alshehri, Faisal N Alotaibi, Rafat Mosalli, Khaled Ali Alawam, Muslim M Alsaadi
April-June 2021, 16(2):188-218
The Saudi Pediatric Pulmonology Association (SPPA) is a subsidiary of the Saudi Thoracic Society (STS), which consists of a group of Saudi experts with well-respected academic and clinical backgrounds in the fields of asthma and other respiratory diseases. The SPPA Expert Panel realized the need to draw up a clear, simple to understand, and easy to use guidance regarding the application of different aerosol therapies in respiratory diseases in children, due to the high prevalence and high economic burden of these diseases in Saudi Arabia. This statement was developed based on the available literature, new evidence, and experts' practice to come up with such consensuses about the usage of different aerosol therapies for the management of respiratory diseases in children (asthma and nonasthma) in different patient settings, including outpatient, emergency room, intensive care unit, and inpatient settings. For this purpose, SPPA has initiated and formed a national committee which consists of experts from concerned specialties (pediatric pulmonology, pediatric emergency, clinical pharmacology, pediatric respiratory therapy, as well as pediatric and neonatal intensive care). These committee members are from different healthcare sectors in Saudi Arabia (Ministry of Health, Ministry of Defence, Ministry of Education, and private healthcare sector). In addition to that, this committee is representing different regions in Saudi Arabia (Eastern, Central, and Western region). The subject was divided into several topics which were then assigned to at least two experts. The authors searched the literature according to their own strategies without central literature review. To achieve consensus, draft reports and recommendations were reviewed and voted on by the whole panel.
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E-cigarettes in the COVID-19 era
Gabriela Gama Freire Alberca, Ricardo Wesley Alberca
April-June 2021, 16(2):219-220
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Demographic and clinical patterns of severe asthma in the Middle East
Mohamed Abuzakouk, Omar Khaled Hassan Attia Ghorab, Bassam Mahboub, Ashraf Alzaabi, Mateen Haider Uzbeck, Mohsen Nasir, Zaid Zoumot, Deepa Grandon, Yaser Abu El Sameed, Rajaie Namas, Ali Saeed Wahla, Jeffrey Chapman, Khaled Saleh, Fulvio Salvo, Govinda Saicharan Bodi, Irfan Shafiq
April-June 2021, 16(2):172-177
BACKGROUND: Severe asthma is a major burden on health-economic resources; hence, knoing the epidemiology of these patients is important in planning and provision of asthma care. In addition, identifying and managing the comorbidities helps improve symptoms and reduce associated morbidity and mortality. OBJECTIVES: Epidemiology of difficult asthma has not been ell studied in the Middle East, so in this study, e present the demographic and clinical characteristics of severe asthma in the United Arab Emirates (UAE). METHODS: We retrospectively revieed the notes of severe asthma patients attending three tertiary care hospitals beteen May 2015 and December 2019. Data on baseline demographics, asthma characteristics, treatment, and comorbidities ere collected. RESULTS: We revieed the notes of 458 patients (271 females and 187 males) that fulfilled the 2019 Global Initiative for Asthma guidelines for the diagnosis of severe asthma. The mean age as 47.7 (standard deviation 17.2) years. Males had significantly higher asthma control test scores (17.9 vs. 16, P = 0.01) and mean blood eosinophils (0.401 vs. 0.294, P <0.01) than females. The most common comorbidity observed as allergic rhinitis (52.2%) folloed by gastroesophageal reflux disease (27.1%). In total, 109 (23.8%) patients ere on biological therapies ith most patients being on omalizumab and dupilumab (29 and 18 patients, respectively). Most patients ere nonsmokers (97.2%), and majority ere of TH2-high phenotype (75.7%). CONCLUSIONS: In this first report of severe asthma characteristics in the UAE, e found a pattern of female preponderance and most patients having a Th2-high phenotype. The findings are likely to help optimize asthma care in the region in the era of biologic therapies.
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Clinical characteristics and outcomes in patients with primary Sjogren's syndrome-associated interstitial lung disease
Esam H Alhamad, Joseph G Cal, Nuha N Alrajhi, Muthurajan P Paramasivam, Waleed M Alharbi, Mohammed AlEssa, Mohammed A Omair, Ammar C AlRikabi, Ahmad A AlBoukai
April-June 2021, 16(2):156-164
BACKGROUND: Diagnosing primary Sjogren's syndrome (pSS)-associated interstitial lung disease (ILD) is complex and can be very challenging. In addition, information about the prognostic factors is limited. AIMS: We aimed to determine the clinical characteristics and prognostic factors that impact pSS-ILD survival. METHODS: This retrospective review included 84 consecutive patients diagnosed with pSS-ILD. The information analyzed included the clinical characteristics, laboratory findings, and physiological and hemodynamic data. Prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: The mean age was 60.5 years, and 61.9% were females. The mean time between the onset of symptoms and diagnosis was 21 months (range, 1–98 months). Minor salivary gland biopsy (MSGB) was positive for pSS in 92.3% of the cohort. Fifty percent of the patients had negative autoimmune serology related to pSS. Based on the available hemodynamic data, 40% had pulmonary hypertension (PH), and 20% had severe PH. During follow-up, acute exacerbation was noted in 38% of the cohort. The 5-year survival rate for all patients was 56%. Male sex, usual interstitial pneumonia pattern, and a reduced forced vital capacity were independent predictors of mortality in the pSS-ILD patients. CONCLUSIONS: A significant delay between the onset of symptoms and diagnosis was noted in our cohort. Importantly, our study highlights the importance of MSGB and emphasizes that clinicians should not rely solely on serological tests to diagnose pSS in ILD patients. The overall survival was poor, and more efforts are needed to diagnose pSS-ILD at an early stage and refer patients to experienced centers.
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A visual analog scale for the assessment of mild sleepiness in patients with obstructive sleep apnea and healthy participants
Yousef D Alqurashi, Aleksander Dawidziuk, Abdullah Alqarni, Julia Kelly, James Moss, Michael I Polkey, Mary J Morrell
April-June 2021, 16(2):141-147
MOTIVATION: Studies have shown poor clinical effectiveness of the Epworth Sleepiness Scale (ESS) due to its ambiguity of items and cultural applicability. This study aimed to investigate the efficacy of a Visual Analog Scale (VAS) to assess sleepiness, compared to ESS. METHODS: Thirty-two obstructive sleep apnea (OSA) patients and 32 healthy participants completed two visits, 1 month apart, during which they completed both ESS and VAS. Patients diagnosed with OSA were treated with Continuous positive airway pressure (CPAP) between visits. The agreement between the ESS and VAS scores in both patients with OSA and healthy participants was investigated using Pearson correlation and Area Under the receiver operating characteristics. RESULTS: The (mean ± standard deviation) Oxygen Desaturation Index for patients with OSA was 18.5 ± 5.7 events/hour and 1.7 ± 1.0 events/hour in the healthy participants. A reduction in sleepiness, following CPAP treatment occurred in patients with OSA, using the ESS (11.2 ± 5.5–4.7 ± 5.0 points, P < 0.001) and the VAS (50.2 ± 3.0–21.9 ± 26.5 mm, P < 0.001). There was no significant change in sleepiness, in healthy participants using the ESS (3.91 ± 3.14–3.34 ± 3.27 points (P < 0.48) or the VAS (15.58 ± 21.21–12.05 ± 14.75 mm, (P < 0.44). A Likert scale showed that the VAS was easier to use compared to ESS in visit 1 (VAS: 8.7 ± 1.9 points, ESS: 7.7 ± 2.6 points, (P < 0.001), and visit 2 (VAS: 9.5 ± 1.4 points, ESS: 8.6 ± 1.5 points, P < 0.001). CONCLUSION: These preliminary results suggest that the VAS can detect a change in sleepiness after CPAP treatment in patients with OSA and that the VAS was also easier to use compared to ESS.
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