Chronic Cough Research Articles

Characteristics, demographics, and epidemiology of possible chronic cough in Sweden: A nationwide register-based cohort study.

To show clinical characteristics, treatments, and comorbidities in chronic cough in a nationwide cohort. Two cohorts were created. A national cohort with individuals from two population-based databases; the National Patient Register and Swedish Prescribed Drug Register. Secondly, a regional cohort including primary care data. Adults with at least one cough diagnosis (ICD-10 R05) and/or individuals with ≥2 dispensed prescriptions for relevant cough-medication within the inclusion period, 2016-2018, were identified. Individuals on medications which may instigate cough or suggest acute infection or diagnosed with conditions where cough is a cardinal symptom, were excluded. Those remaining were defined as having possible refractory or unexplained chronic cough (RCC/UCC). Altogether 62,963 individuals were identified with possible RCC/UCC, giving a national prevalence of about 1%. Mean age was 56 years and 60% were females. Many (44%) of the individuals with possible RCC/UCC visited cough relevant specialist clinics during the study period, but less than 20% received a cough diagnosis. A majority (63%) had evidence of RCC/UCC in the 10 years prior to inclusion in the study. In the regional cohort, including primary care data, the prevalence of RCC/UCC was doubled (2%). Cough medicines were mainly prescribed by primary care physicians (82%). Most individuals with possible RCC/UCC sought medical care in primary care, and had a long history of cough, with various treatments tried, indicating a substantial burden of the condition. Referrals to specialist care were very rare. The results underline the need for a structured multidisciplinary approach and future therapeutic options.

Oesophageal adenocarcinoma presenting as a foreign body induced intrathoracic abscess in a dog

AbstractA 9‐year‐old, male, entire Irish setter was referred for further investigation of a chronic cough, anorexia, weight loss and lethargy. Computed tomography revealed a large ovoid encapsulated lesion, with a gas and fluid attenuating centre, and an intralesional mineral opacity. The lesion ran close to the caudal oesophagus, and extended cranially within the pulmonary parenchyma. Endoscopy revealed a communication between the lumen of the distal oesophagus and the lesion, which contained a purulent discharge and plant material. Based on the computed tomography and endoscopic findings, the diagnosis was expected to be a thoracic abscess, secondary to foreign body migration or penetration; however, surgical resection and histopathological analysis of the lesion revealed an oesophageal adenocarcinoma. This case details the unusual presentation of an oesophageal adenocarcinoma, with endoscopic and computed tomography findings that mimicked a thoracic abscess with an intralesional foreign body.

RELATIONSHIP BETWEEN SYNTHETIC COTTON DUST EXPOSURE AND SYMPTOMS OF RESPIRATORY DISORDERS IN TEXTILE FACTORY WORKERS AT PT X IN EAST JAVA

Introduction. Respiratory disorders, which range from 1 to 100 μm, are a significant concern in the textile industry. Typical symptoms of cotton dust exposure include chronic cough with or without phlegm, painful breathing, wheezing, nasal congestion, and chest pain. While most research has focused on natural cotton fibers, there is a growing need to investigate the health risks associated with synthetic cotton dust, such as that derived from petroleum-based resources such as polyester. Method. This research employed a cross-sectional design, with 76 respondents. Result & Analysis. The results showed that 21.1% of the workers experienced respiratory symptoms, and 43.4% of the workers were exposed to high levels of synthetic cotton dust. Chi-square test analysis indicated a significant relationship between synthetic cotton dust exposure and respiratory symptoms (p < 0.001; OR 15.1 [3.17 – 73.21]). Discussion. Workers with high synthetic cotton dust exposure had a 15.1 times greater risk of experiencing respiratory symptoms than those with low synthetic cotton dust exposure.

A systematic review of the psychometric properties of the Leicester Cough Questionnaires based on the COSMIN guidelines

BackgroundChronic cough affects around 10 % of the general adult population, impairing all aspects of quality of life. Research questionWhat are the Leicester Cough Questionnaire's psychometric properties? Study design and methodsElectronic searches of PubMed, CINAHL, and ScienceDirect databases were conducted from inception until October 1rst 2022. All full-text articles, published in French or English, aimed at evaluating the LCQ's content validity or psychometric properties were included. The COSMIN Risk of Bias checklist was applied to assess their methodological quality and results. Results were qualitatively summarised and rated by a modified GRADE approach. Results40 studies were included accounting for 8731 adults, subject to cough or a respiratory condition. Chronic cough (>8 weeks) was the most represented. The LCQ's total score is relevant and comprehensible for the assessment of the impact of cough on QoL. The original 3-factor model showed a satisfactory model fit. Good convergent validity was found for the total and physical domain scores. These scores demonstrate good internal consistency and test retest reliability, with some variability noted and they are responsive to change. Recent estimates of MID thresholds were 1.7 and 0.4 for total and domain scores respectively. The quality of the studies is globally poor. InterpretationThe LCQ is a valid outcome to assess the intra-individual impact of cough on QoL and to detect large changes in quality of life mainly in a short-term clinical trial setting. Clinical trial registrationThe protocol was registered with PROSPERO (CRD42022355191).

Management of multiple pelvic organ prolapse due to pulmonary tuberculosis in a suburban hospital: A case report

Pelvic organ prolapse (POP) is a condition in which the pelvic organs herniate into the vaginal canal or the vaginal introitus due to weakness of the pelvic floor support structures. The occurrence of POP is prevalent, especially in older women, with various other risk factors, including multiparity, obesity, menopause, malignancy, and chronic infections. We report a unique and rare case in which uterine prolapse was followed by cystocele and rectocele with the risk factors of advanced age, menopause, and chronic cough in a 73-year-old female who complained of a chronic cough for 2 months. When coughing, the patient experienced a protrusion coming out, especially from the vaginal canal. Other complaints included night sweats, urinary problems, and constipation. Additional sounds identical to fine rhonchi were found on auscultation examination in both lung fields. On examination of the external genitalia, a pink protrusion came out of the vaginal introitus, approximately the size of a chicken egg, accompanied by the hyperemic rectal mucosa protrusion through the anal canal. Chest X-ray results confirmed that there was an active tuberculosis infection.

Abnormal breathing pattern features in chronic refractory cough

Abnormal breathing pattern features in chronic refractory cough

Double tracheoesophageal fistula after prolonged intubation during COVID-19: surgical treatment by colonic transposition in the retrosternal space

This is a patient with 2 tracheoesophageal fistulas following prolonged intubation due to COVID-19 with severe evolution and indication for surgical treatment due to failure of endoscopic treatment. Patient in a long hospital stay, unable to eat an oral diet, malnourished, chronic cough, developing persistent pneumonia due to recurrent salivary bronchoaspiration. The case was treated by complex surgical intervention consisting of proximal and distal partial esophagectomy with reconstruction of food transit by colonic bypass in the anterior mediastinum, resection and tracheal reanastomosis. The final result was good, with the patient being discharged from the hospital on a restored oral diet and free spontaneous breathing. The resolution of an extremely serious case through a complex and exceptional surgical approach, which imposed enormous challenges in pre-operative preparation and detailed therapeutic planning, with single-stage surgical action by two surgical teams (Digestive System Surgery and Thoracic Surgery).

Chronic cough as a disease

Chronic cough is a frequent reason for medical consultation and has significant impact on quality of life. Due to the limited effectiveness of currently available treatments, and delays in accessing care, patients are often inadequately managed. There also remains an overreliance by clinicians on outdated management algorithms, addressing chronic cough only as symptom of other medical conditions, and advocating investigation and trials of treatment of diseases which are often not present. This may lead to unnecessary cost, frustration, and potential harm. Newer clinical guidelines in essence consider chronic cough as a disease in itself, resulting from afferent neuronal hypersensitivity and central nervous system dysfunction. Secondary factors which aggravate chronic cough (smoking, asthma, gastroesophageal reflux, etc), are better considered as treatable traits associated with the primary disease process rather than direct “causes” of cough.Explicitly approaching chronic cough as a discrete entity is consistent with the way in which “diseases” are generally characterised, and has advantages. The patient should be better able to understand their condition, and may have better confidence in attempts at management. The clinician should have better focus and avoid unfruitful treatments and investigation. In general, considering chronic cough as a disease should also help to raise the profile of the condition, improve organisation of health service pathways, increase attention for research, and further the development of new treatments.

The development of the Cough Hypersensitivity Questionnaire (CHQ) for chronic cough

IntroductionChronic cough is considered a disorder of neuronal hypersensitivity in which patients frequently report abnormal laryngeal and chest sensations, and excessive triggers. To facilitate clinical assessment we developed the Cough Hypersensitivity Questionnaire (CHQ).MethodsCandidate questionnaire items were developed following interviews with patients with refractory chronic cough (n=10, United Kingdom), and review by a multidisciplinary team. The CHQ was evaluated in individuals with chronic cough (n=535, UK/South Korea), for uni-dimensionality and differential item functioning (with Rasch Analysis), internal consistency, concurrent validity (against cough severity visual analogue scale (VAS) and Leicester Cough Questionnaire (LCQ) scores), and content validity (cognitive debriefing interviews, n=13).ResultsConcept elicitation created a pool of 34 items. Eleven were removed following multidisciplinary team review of patient interviews. Rasch analysis confirmed the CHQ total score to be a unidimensional scale; one item was removed due to differential item functioning. The final 22 binary-item CHQ comprises 6 sensation-related and 16 trigger-related items.Median (IQR) total CHQ scores were 9 (6–12); sensations 4 (2–5), triggers 5 (3–8). Internal consistency was good (person separation index 0.74). The CHQ total score was moderately associated with cough severity VAS (0.42, p=0.005) and LCQ total score (ρ=−0.52, p<0.001). In cognitive debriefing, patients found the CHQ relevant to their condition and simple to complete.ConclusionThe CHQ is simple to use and has validity for assessing cough triggers and sensations in patients with chronic cough. Further studies are needed to assess its repeatability, responsiveness, and clinical utility.

An observational study to understand burden and cost of care in adults diagnosed with refractory chronic cough (RCC) or unexplained chronic cough (UCC)

BackgroundRefractory and unexplained chronic cough (RCC and UCC) necessitate frequent referral for specialist evaluations, but data on healthcare resource utilisation and costs are lacking.MethodsThis observational study enrolled adults with RCC or UCC attending a specialist cough clinic and included a control cohort, both from North West England, matched 1:5 for age, gender and smoking history. Primary and secondary care data were obtained for the 5 years prior to and 2 years post initial clinic visit (index). The primary endpoint was the total 5-year healthcare cost to the UK NHS pre-RCC or UCC diagnosis compared to the control cohort.ResultsMean age at index for the 200 RCC or UCC consented patients was 62.2 ± 11.4 years; 71% were female, and 68% had never smoked. Mean duration of symptoms pre-diagnosis was 8.0 ± 9.4 years. Mean cough severity score was 63.7 ± 23.2 mm at index on a Visual Analog Scale, and Leicester Cough Questionnaire total score was 10.9 ± 4.1. GP data were available for 80 patients and mean total cost over the 5 years pre-diagnosis (index date) was 3.0-fold higher (95% CI 2.3, 3.9) than in the control cohort (p < 0.001). Most excess costs were related to visits and procedures carried out in secondary care. RCC- or UCC-associated costs decreased post-diagnosis, but remained higher than those of controls.ConclusionDiagnosis of RCC or UCC requires significant health resource utilisation in the 5 years prior to a specialist clinic diagnosis. Resource utilisation was less after diagnosis, but remained higher than in a matched control cohort.

Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency.

Treatment of chronic cough remains a challenge. We hypothesised that inhaled alkaline hypertonic divalent salts (alkaline HDS) might provide relief for refractory chronic cough by laryngeal and tracheal hydration. We conducted an exploratory, single-blinded, nasal saline-controlled study in 12 refractory chronic cough patients to examine cough suppression efficacy of an alkaline HDS composition (SC001) at pH 8 or pH 9 administered by nasal inhalation. As control, we used nasal saline with the same hand-held pump spray aerosol device. Each subject was monitored continuously using a digital cough monitor watch for 1 week of baseline, 1 week of control treatment and 1 week of active treatment. Baseline daily cough rates ranged from 4 to 34 coughs·h-1 with mean visual analogue score 65±17 pre- and post-baseline testing. Control-adjusted efficacy of cough rate reduction ranged from 15% (p=0.015) (from Day 1) to 23% (p=0.002) (from Day 3). Control-adjusted efficacy was highest with SC001 pH 9 (n=5), ranging from 25% (p=0.03) (from Day 1) to 35% (p=0.02) (from Day 3), and lowest for SC001 pH 8 (n=7), ranging from 9% (p=0.08) (from Day 1) to 16% (p=0.02) (from Day 3). Hourly cough counts and visual analogue score correlated for baseline (r=0.254, p=0.02) and control (r=0.299, p=0.007) monitoring weeks. Treatment improved this correlation (r=0.434, p=0.00006). No adverse events were reported. Alkaline (pH 9) HDS aerosol is a promising treatment for refractory chronic cough and should be further evaluated.

Prevalence and disease burden of chronic cough in nine cities of China: an observational study

BackgroundChronic cough (CC) is common in the general population of China, creating a difficult-to-ignore public health burden. However, there is a lack of research on the nationwide prevalence and disease burden of CC in the Chinese population. We aim to use an insurance claims database to assess the prevalence and the corresponding economic burden owing to CC in China.MethodsThis was a retrospective observational study based on an administrative medical insurance database in 2015, 2016 and 2017, from nine cities in North, South, East, South-West, and North-West regions of China. The study population was Chinese adults (≥ 18 years old) who had been identified as CC patients. Descriptive data analyses were used in statistical analysis.ResultsA total of 44,472, 55,565, and 56,439 patients with mean ages of 53.2 (16.3) years were identified as patients with CC in 2015, 2016, and 2017, respectively. Of these, 55.24% were women. In addition, 8.90%, 9.46%, and 8.37% of all patients in 2015, 2016, and 2017, who had applied for medical insurance, had CC, respectively, with a three-year average probability of 8.88%. The median number of outpatient visits within a calendar year was 27 per year due to any reason during the period of 2015–2017. The median medical cost of each patient per year increased from 935.30 USD to 1191.47 USD from 2015 to 2017.ConclusionCC is common among medical insurance users, with a substantial utilization of medical resources, highlighting the huge burden of CC in China.

Londrina Activities of Daily Living Protocol: validity, reliability, minimal detectable change, and standard error of measurement in adults with asthma

Introduction Asthma symptoms are dyspnea, chronic cough, wheezing, chest tightness, or chest discomfort, which can directly limit the activities of daily living (ADL), which is frequently reported by adults with asthma. Evaluating ADL with a reliable protocol at the usual speed is necessary. Objectives To investigate the validity, reliability, minimal detectable change (MDC), and standard error of measurement (SEM) of the Londrina ADL Protocol (LAP) for adults with asthma. Methods Adults with asthma were evaluated with the LAP test. Spearman’s correlation coefficient was used to verify validity with the 6-min walk test (6MWT), Glittre-ADL test, and London Chest Activity of Daily Living (LCADL). To test the reliability, the test was reapplied in at least 30 min; the Wilcoxon test and Intraclass Correlation Coefficient (ICC), SEM, MDC, and learning effect were performed. Results Fifty-three individuals were included (26% men, 43 ± 15 years, BMI 28 ± 8 kg/m2, FEV1 70 ± 24%predicted). For convergent validity, the LAP test was correlated with the 6MWT, Glittre-ADL, and LCADL scale (r = −0.49, 0.71, and 0.30, respectively; p < 0.03). There was a difference in test-retest (p < 0.0001) and reliability analysis shows ICC3 of 0.94, SEM of 14.88 s (22%), and MDC of 41.23 s (15%). Furthermore, the individuals performed the second test with −23 ± 19 (7.9%) s. Conclusion The LAP test is valid and reliable for assessing limitations during ADL in adults with asthma. Considerable learning effect was observed, therefore, the best of two measures may avoid underestimation.

A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.

Nalbuphine (NAL) is a κ-agonist/μ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR). Clinical pharmacokinetic (PK) data sets in healthy subjects from three trials that included IV, oral solution, and ER tablets in fed and fasted state and two published trials were used to parametrize a novel partial differential equation (PDE)-based model, termed "PDE-EHR" model. Experimental inputs included in vitro dissolution and permeability data. The model incorporates a continuous intestinal absorption framework, explicit liver and gall bladder compartments, and compartments for systemic drug disposition. The model was fully PDE-based with well-stirred compartments achieved by rapid diffusion. The PDE-EHR model accurately reproduces NAL concentration-time profiles for all clinical data sets. NAL disposition simulations required inclusion of both parent and glucuronide recirculation. Inclusion of intestinal P-glycoprotein efflux in the simulations suggests that NAL is not expected to be a victim or perpetrator of P-glycoprotein-mediated drug interactions. The PDE-EHR model is a novel tool to predict EHR and food/formulation effects on drug PK. The results strongly suggest that even intravenous dosing studies be conducted in fasted subjects when EHR is suspected. The modeling effort is expected to aid in improved prediction of dosing regimens and drug disposition in patient populations.

Alteration of the airway microbiota is associated with the progression of post-COVID-19 chronic cough in adults: a prospective study

Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.

Diagnostic value of the pepsin concentration in saliva and induced sputum for gastroesophageal reflux-induced chronic cough: a prospective clinical study.

Finding a simple, effective and rapid diagnostic method to improve the diagnosis of gastroesophageal reflux-induced chronic cough (GERC) is indicated. Our objective was to determine the diagnostic value of the pepsin concentration in saliva and induced sputum for GERC. 171 patients with chronic cough were enrolled. The diagnosis and treatment followed the chronic cough diagnosis and treatment protocol. Saliva and induced sputum were collected, and the pepsin concentration was determined using Peptest. A Gastroesophageal Reflux Diagnostic Questionnaire (GerdQ) was completed. The diagnostic value of the pepsin concentration in saliva and induced sputum for GERC was analysed and compared. The salivary pepsin concentration predicted GERC with an area under the receiver operating characteristic curve (AUC) of 0.845. The optimal cut-off value was 76.10 ng·mL-1, the sensitivity was 83.58% and the specificity was 82.69%. The pepsin concentration in the induced sputum supernatant for GERC had an AUC of 0.523. When GerdQ was used for GERC diagnosis, the AUC was 0.670 and the diagnostic value of salivary pepsin was better compared to GerdQ (DeLong test, p=0.0008). Salivary pepsin had a comparable diagnostic value to GerdQ (AUC 0.779 versus 0.826; p=0.4199) in acidic GERC. Salivary pepsin had superior diagnostic value compared to GerdQ (AUC 0.830 versus 0.533; p<0.0001) in non-acidic GERC. A salivary pepsin concentration >76.10 ng·mL-1 is of good diagnostic value for GERC, especially in non-acidic GERC. The pepsin concentration in induced sputum has a low diagnostic value.

Need for sex-stratified reference values for exhaled nitric oxide as biomarker in chronic cough.

The implementation of exhaled nitric oxide fraction (F ENO) as a biomarker in patients with chronic cough requires sex-stratified F ENO reference values in general and sex-stratified cut-off levels in the management of unexplained chronic cough https://bit.ly/3JHi0vb.

Primary Mucoepidermoid Carcinoma of Trachea − A Rare Cause of Chronic Cough in the Young

Primary Mucoepidermoid Carcinoma of Trachea − A Rare Cause of Chronic Cough in the Young

Aspergillus oryzae Isolated from Lung Tissue Sample in a Chronic Respiratory Illness Patient from South India

Opportunistic fungal infection by Aspergillus oryzae in patients with chronic respiratory condition is rare in India. A 52-year-old male with a history of diabetes mellitus, chronic smoking, and alcoholism presented with chronic cough, breathlessness, and recurrent blood in sputum. CT imaging revealed features consistent with old pulmonary tuberculosis sequelae and the presence of a right lung lower lobe aspergilloma. The patient underwent a right lower lobectomy, and histopathological examination confirmed severe acute and chronic bronchiolitis with bronchiectasis and organizing pneumonia, indicative of fungal ball formation. Microbiological analysis identified Aspergillus species, possibly A. flavus complex, with sequencing confirming A. oryzae. This case is unique as A. oryzae is typically associated with food fermentation and rarely implicated in invasive lung infections, especially outside regions of traditional exposure, like Japan. The rarity of this presentation underscores the importance of considering unusual pathogens in clinical practice and utilizing advanced diagnostic techniques such as sequencing for accurate identification. The successful outcome of this case, with prolonged antifungal therapy based on microbiological confirmation and clinical follow-up, suggests the importance of personalized treatment strategies. This case report adds to the growing body of evidence on the clinical significance and pathogenic potential of A. oryzae. It underscores the importance of continued vigilance and research in fungal infections.

FEATURES OF ANESTHESIA IN PATIENTS WITH SPECIAL NEEDS. PART 1

The non-medical use of cannabis can negatively impact the morpho-functional state of almost all organs and systems of the human body. During acute intoxication and established drug dependence, it can unevenly distort the effects of drugs for local and general anesthesia, leading to life-threatening complications. Part 1 of this review presents the results of acute and chronic cannabis use on homeostasis. Cerebral vasospasm and atherosclerosis are identified as major etiological factors for cannabis-related cerebrovascular diseases. Young to middle-aged individuals (30–50 years), male gender (male-to-female ratio 3.7:1), and chronic use (86%) are significant independent predictors of neurovascular toxicity, cerebral hypoperfusion, and stroke. Cannabis smoking causes damage to the respiratory mucosa similar to tobacco. Regular cannabis smokers can expect irritation of the upper respiratory tract, swelling, obstruction, chronic cough, bronchitis, lung emphysema, and bronchospasm. Some reports advocate the use of dexamethasone during surgery to alleviate these symptoms. The detrimental effects of chronic cannabis use on liver and kidney functions are somewhat overstated. Disturbances in immune system, thermoregulation, blood clotting, and carbohydrate metabolism in the absence of anesthetic precautions can significantly complicate the patient's condition in the perioperative period. Cannabinoids can interact with drugs from various groups. Awareness of the pathophysiological and biochemical consequences of cannabis use allows anesthesiologists to anticipate and effectively manage perioperative complications in this patient category