Profiles of Cough and Associated Risk Factors in Nonhospitalized Individuals With SARS-CoV-2 Omicron Variant Infection: Cross-Sectional Online Survey in China.

BACKGROUND: Cough is a common symptom during and after COVID-19 infection; however, few studies have described the cough profiles of COVID-19. OBJECTIVE: The aim of this study was to investigate the prevalence, severity, and associated risk factors of severe and persistent cough in individuals with COVID-19 during the latest wave of the Omicron variant in China. METHODS: In this nationwide cross-sectional study, we collected information of the characteristics of cough from individuals with infection of the SARS-CoV-2 Omicron variant using an online questionnaire sent between December 31, 2022, and January 11, 2023. RESULTS: There were 11,718 (n=7978, 68.1% female) nonhospitalized responders, with a median age of 37 (IQR 30-47) years who responded at a median of 16 (IQR 12-20) days from infection onset to the time of the survey. Cough was the most common symptom, occurring in 91.7% of participants, followed by fever, fatigue, and nasal congestion (68.8%-87.4%). The median cough visual analog scale (VAS) score was 70 (IQR 50-80) mm. Being female (odds ratio [OR] 1.31, 95% CI 1.20-1.43), having a COVID-19 vaccination history (OR 1.71, 95% CI 1.37-2.12), current smoking (OR 0.48, 95% CI 0.41-0.58), chronic cough (OR 2.04, 95% CI 1.69-2.45), coronary heart disease (OR 1.71, 95% CI 1.17-2.52), asthma (OR 1.22, 95% CI 1.02-1.46), and gastroesophageal reflux disease (GERD) (OR 1.21, 95% CI 1.01-1.45) were independent factors for severe cough (VAS>70, 37.4%). Among all respondents, 35.0% indicated having a productive cough, which was associated with risk factors of being female (OR 1.44, 95% CI 1.31-1.57), having asthma (OR 1.84, 95% CI 1.52-2.22), chronic cough (OR 1.44, 95% CI 1.19-1.74), and GERD (OR 1.22, 95% CI 1.01-1.47). Persistent cough (>3 weeks) occurred in 13.0% of individuals, which was associated with the risk factors of having diabetes (OR 2.24, 95% CI 1.30-3.85), asthma (OR 1.70, 95% CI 1.11-2.62), and chronic cough (OR 1.97, 95% CI 1.32-2.94). CONCLUSIONS: Cough is the most common symptom in nonhospitalized individuals with Omicron SARS-CoV-2 variant infection. Being female, having asthma, chronic cough, GERD, coronary heart disease, diabetes, and a COVID-19 vaccination history emerged as independent factors associated with severe cough, productive cough, and persistent cough.

Diagnostic accuracy of blood eosinophils in comparison to other common biomarkers for identifying sputum eosinophilia in patients with chronic cough.

Background: Sputum eosinophilia is a treatable trait for chronic cough. It is currently not clear whether the blood eosinophil counts could be used to identify sputum eosinophilia in patients with chronic cough. This study aimed to evaluate the diagnostic accuracy of blood eosinophils in comparison to other common type 2 biomarkers for identifying sputum eosinophilia in patients with chronic cough. Methods: In this prospective study, a total of 658 patients with chronic cough were enrolled. Induced-sputum test, routine blood test, total immunoglobulin E (TIgE), and fractional exhaled nitric oxide (FeNO) level were measured. The percentage of sputum eosinophils (Eos%) ≥ 2.5% was defined as sputum eosinophilia. The area under the curve (AUC) of blood eosinophil counts, TIgE, and FeNO alone or in combination for predicting sputum eosinophilia were analyzed. Results: The AUC of blood eosinophil counts for predicting sputum eosinophilia in chronic cough patients was moderate [0.826 (0.767-0.885)], as compared to that of FeNO [0.784 (0.720-0.849), P = 0.280] and TIgE [0.686 (0.613-0.760), P = 0.001]. When combining blood eosinophil counts and FeNO for detecting sputum eosinophilia, a significantly larger AUC [0.868 (0.814-0.923), with a sensitivity of 84.2% and a specificity of 82.8%] was yielded, as compared to each single marker alone (all P < 0.05). Conclusions: Blood eosinophil counts have a moderate diagnostic value for identifying sputum eosinophilia in patients with chronic cough, while a combination of blood eosinophil counts and FeNO measurement can provide additional predictive value.

Clinical characteristics of protracted bacterial bronchitis in adults.

There are few data regarding adult protracted bacterial bronchitis (PBB). This study aimed to delineate the clinical features of PBB and evaluate their potential diagnostic value in adults. We recruited 55 adult patients with PBB and selected randomly 220 patients with non-PBB as control. A diagnosis of PBB was considered if patients had a cough lasting ≥3 weeks, no abnormalities of chest computed tomography, positive bacterial culture in sputum and/or response well to oral moxifloxacin for 1-4 weeks. The clinical manifestations and laboratory investigations were compared between PBB patients and non-PBB patients. Of the 55 patients with PBB, approximately three-fifths (34, 61.8%) were females with a median age of 46.0 years, which were similar to that of patients with non-PBB. We observed a shorter cough duration in PBB than non-PBB (median 3.0 versus 24.0 months, p < 0.001). Compared to non-PBB patients, PBB patients had higher incidences of productive cough, yellow phlegm and a sensation of mucus in the throat (SMIT) (all p < 0.001). Sputum neutrophils and lymphocytes were markedly elevated in PBB patients than non-PBB patients (both p = 0.004). Bacterial pathogens were detected in eight (28.6%) of 28 cases with PBB. The multivariate analyses showed yellow phlegm, productive cough, SMIT, increased sputum lymphocytes (≥2.3%) and cough duration ≤8.5 months with moderate sensitivity (50.9-81.8%) and moderate-high specificity (60.5-94.4%) for determining PBB. In summary, adults with PBB are characterized by productive cough, yellow phlegm, SMIT and neutrophilic airway inflammation. These cough features and increased sputum lymphocytes may be useful to indicate PBB.

Aspergillus tracheobronchitis with Birt-Hogg-Dubè syndrome as a rare cause of chronic cough.

BACKGROUND: Aspergillus tracheobronchitis (ATB) is confined as a condition of chronic superficial infection of tracheobronchial tree. Its diagnosis is difficult due to atypical manifestations and low detective rate of Aspergillus thus far. CASE PRESENTATION: Herein, we presented a 45-year-old male patient with a sole chronic productive cough for five years referred to our cough specialist clinic. Chest high-resolution computed tomography showed multiple lung cysts predominantly located in the subpleural lesions and near the mediastinum. Neither bacteria nor fungi were identified by sputum culture. However, metagenomic next-generation sequencing in sputum detected Aspergillus fumigatus DNA. The genetic testing of whole blood suggested the germline mutation of the tumor suppressor gene folliculin, supporting a diagnosis of Birt-Hogg-Dubé (BHD) syndrome. His productive cough symptom significantly improved after receiving itraconazole treatment for 2 months. After discontinuation of antifungal treatment, there was no relapse for four months follow-up. A diagnosis of ATB with BHD syndrome was eventually established in this patient. CONCLUSION: ATB should be considered in any patient with prolonged unexplained productive cough. Next-generation sequencing technologies may be useful to identify ATB which is uncommon and easily ignored in clinical practice.

A multicenter survey on the current status of chronic cough and its impact on quality of life in Guangdong, China.

Background: Chronic cough is a troublesome clinical problem with long-term impacts at the patient level. However, the burden of chronic cough in China is largely unknown. Thus, we performed a multicenter cross-sectional survey on the current status of chronic cough and its impact on quality of life in Guangdong, south China. Methods: Using a standardized questionnaire, we extracted and analyzed the relevant data on demographics, number of visits to a doctor, previous diagnosis, previous medications used and initial diagnosis. Cough-specific quality of life was measured by the Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC). Results: Of 933 patients from 13 tertiary medical centers in Guangdong, 52.2% were female, the median age was 40.0 [interquartile range (IQR), 31.0-52.0] years, and the median duration of chronic cough was 6.0 (IQR, 3.0-24.0) months. Over half (n=452, 54.0%) of the patients had visited physicians ≥3 times for cough. In terms of previous diagnosis, bronchitis (n=432, 46.5%) had been most frequently diagnosed, followed by pharyngitis (n=246, 26.5%) and asthmatic cough (n=98, 10.5%). A majority of patients with chronic cough had used antitussive agents (n=539, 58.5%), antibiotics (n=374, 40.6%) and traditional Chinese medicine (TCM) (n=294, 31.9%). Among the three subscales of the LCQ-MC, we observed lower scores in the mental health domain than in the physical and social domains (both P<0.001). Additionally, lower LCQ-MC scores were found in females and patients who saw the doctor >3 times for both the total and three subscale scores (all P<0.05). Conclusions: Misdiagnosis and inappropriate treatment are prevalent in patients with chronic cough and lead to considerable antibiotic abuse. Chronic cough markedly affects suffers' quality of life, especially for women.

Clinical characteristics of patients with chronic cough in Guangdong, China: a multicenter descriptive study.

BACKGROUND: The clinical characteristics of patients with chronic cough are reported only in single-center survey in China, being significantly different from that in western countries. Here, we performed a multicenter study to describe the clinical characteristics of chronic cough patients. METHODS: A cross-sectional observational survey was conducted in thirteen tertiary hospitals of Guangdong, South China. Relevant data were recorded using a standardized questionnaire and analyzed, including demographics, educational attainment, cough features, and concomitant symptoms. RESULTS: Of 933 patients in this study, the median age was 40.0 (IQR 31.0-52.0) years with a peaked age of 30-39 years. The proportion of females (487, 52.2 %) was comparable to that of males (446, 47.8 %). Up to 81.9 % of the patients were non-smokers. More than two-thirds of the subjects with chronic cough had a low educational level. The median cough duration was 6.0 (IQR 3.0-24.0) months, and 73.0 % of chronic cough patients presented with dry cough. Laryngeal paresthesia was the most common concomitant symptom (704, 75.5 %), followed by rhinitis/sinusitis-related (350, 37.5 %) and respiratory symptoms (322, 34.5 %). Rhinitis/sinusitis-related symptoms more frequently occurred in patients with productive cough than in those with dry cough (49.0 % vs. 33.0 %, P < 0.001). Moreover, female patients displayed an older age and a higher prevalence of nocturnal cough compared to male patients (both P < 0.05). CONCLUSIONS: Our results show an equal gender, young profile and laryngeal paresthesia in patients with chronic cough, and different clinical features between females and males.

The spectrum, clinical features and diagnosis of chronic cough due to rare causes.

BACKGROUND: Chronic cough has many diverse causes, including common and uncommon causes. There are few comprehensive reports on rare causes of chronic cough. The purpose of this study is to determine the etiological distribution, clinical features, and diagnostic value of special examinations in patients with rare causes of chronic cough. METHODS: A retrospective analysis of patients with chronic cough who underwent medical history taking, full examination, and etiological treatment over a 13-year period was conducted. Causes of chronic cough with a prevalence of less than 3% were defined as rare causes. RESULTS: A total of 1,554 patients were enrolled, and 39 causes of chronic cough were identified. Among them, 1,055 cases were due to common causes, whereas 235 cases were due to rare causes; the causes involved 7 bodily systems. The top five rare causes were protracted bacterial bronchitis, somatic cough syndrome, diffuse panbronchiolitis, obstructive sleep apnea syndrome (OSAS), and interstitial lung disease, accounting for 67.2% of all rare causes. Among 235 patients with rare causes, causes in 90 (38.3%) patients were detected by chest high-resolution computed tomography (HRCT), in 44 (18.7%) patients by bronchoscopy/nasopharyngoscopy, and in 21 (8.9%) patients by pulmonary spirometry and diffusing capacity testing. CONCLUSIONS: Among the 31 rare causes of chronic cough in this cohort, the top five were protracted bacterial bronchitis, somatic cough syndrome, diffuse panbronchiolitis, OSAS, and interstitial lung disease. Special examinations, such as chest HRCT and bronchoscopy, should be considered after excluding common causes of chronic cough.

The efficacy and safety of azithromycin in chronic respiratory diseases related cough.

BACKGROUND: Azithromycin is potential for preventing exacerbations in chronic respiratory diseases. However, rare attention was paid to the cough symptom of such airway diseases by azithromycin intervention. We summarized the efficacy and safety of azithromycin in chronic respiratory diseases related cough. METHODS: We searched 4 electronic databases (PubMed, EMBASE, Cochrane, and Web of Science) to identify randomized controlled trials (RCTs) comparing the change of Leicester Cough Questionnaire (LCQ) score, cough visual analogue scale (VAS) and side effects of azithromycin in patients of chronic respiratory diseases with cough. RESULTS: We identified 5 RCTs (n=879 patients) in pooled analyses. Compared to placebo, azithromycin intervention had no effect in reducing cough [mean difference (MD) 0.73; 95% CI: -0.78 to 2.24; P=0.34] with significant heterogeneity (P=0.03, I2 =71%). However, heterogeneity is caused by one study. After removal of this study, azithromycin administration had shown clinically important improvement in LCQ score (MD 1.30; 95% CI: 1.15-1.46; P<0.00001; I2 =0%). In addition, no significant difference was detected in adverse events and azithromycin administration probably had less central nervous system side effects for chronic respiratory diseases with cough. CONCLUSIONS: The addition of oral azithromycin may result in significant benefit for chronic respiratory diseases related cough. Azithromycin was safe for those patients with cough.