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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 9
| Issue : 2 | Page : 101-106 |
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Chronic cough etiology within a tertiary care center: A retrospective chart review
Krittin J Supapannachart1, Amanda S Fryd1, Sandeep Shelly2, Anjali Warrier3, Andrew Tkaczuk4, Jeanne L Hatcher4, Adviteeya N Dixit5, Keriann M Van Nostrand5, Anand S Jain6, Amanda I Gillespie2, Merin K Kalangara7, Adam M Klein4
1 Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA
2 Emory Voice Center; Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA
3 GCS Medical College, Ahmedabad, Gujarat, India
4 Department of Otolaryngology, Emory University School of Medicine; Emory Voice Center; Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, USA
5 Department of Otolaryngology, Emory University School of Medicine; Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
6 Department of Otolaryngology; Department of Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA
7 Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| Date of Submission | 10-Jun-2022 |
| Date of Decision | 29-Sep-2022 |
| Date of Acceptance | 02-Oct-2022 |
| Date of Web Publication | 29-Oct-2022 |
Correspondence Address:
Dr. Adam M Klein
550 Peachtree Street NE, Atlanta, Georgia 30308
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijamr.ijamr_133_22
Purpose: Chronic cough occurs in 12% of the population and is associated with significant morbidity and healthcare utilization. Little is known about chronic cough patients requiring referral to higher level care facilities; such knowledge may improve primary care physician chronic cough referral algorithms. Methods: A retrospective study was conducted on patients with primary complaints of chronic cough presenting to Emory Healthcare, Atlanta between 2009 and 2020. Data on socio-demographics, etiology, treatment, and health behavior were extracted from the electronic medical records of patients with chronic cough that had been seen by at least by 1 cough specialist at a tertiary care center. The Chi-square test and analysis of variance helped determine differences in socio-demographic variables between patients with different primary cough etiologies. Results: A total of 1152 patients met the inclusion criteria for this study. Common etiologies of chronic cough were found to be neurogenic (n = 196, 17%), gastroesophageal reflux disease (n = 114, 9.9%), asthma (n = 93, 8.1%), and chronic obstructive pulmonary disease (n = 80, 6.9%). A multifactorial etiology was found in 213 (18.5%) patients and 99 (8.6%) patients were still undergoing further work up. Significant differences in age, sex, race, smoking status, and chronic cough duration were noted based on the underlying etiology. Interestingly, although nonsignificant, patients with pulmonary etiologies tended to live in areas with higher poverty rates. Conclusion: The most common etiology was neurogenic cough, typically a diagnosis of exclusion that goes undiagnosed in primary care settings. Primary care physicians should have a low threshold for referral to otolaryngologists and academic institutions should consider establishing multidisciplinary cough clinics to facilitate work up and treatment.
Keywords: Chronic cough, chronic disease, ear, nose, and throat, epidemiology, multidisciplinary care, population health, respiratory diseases
How to cite this article:
Supapannachart KJ, Fryd AS, Shelly S, Warrier A, Tkaczuk A, Hatcher JL, Dixit AN, Van Nostrand KM, Jain AS, Gillespie AI, Kalangara MK, Klein AM. Chronic cough etiology within a tertiary care center: A retrospective chart review. Int J Adv Med Health Res 2022;9:101-6 |
How to cite this URL:
Supapannachart KJ, Fryd AS, Shelly S, Warrier A, Tkaczuk A, Hatcher JL, Dixit AN, Van Nostrand KM, Jain AS, Gillespie AI, Kalangara MK, Klein AM. Chronic cough etiology within a tertiary care center: A retrospective chart review. Int J Adv Med Health Res [serial online] 2022 [cited 2023 Apr 2];9:101-6. Available from: https://www.ijamhrjournal.org/text.asp?2022/9/2/101/360033 |
| Introduction | |  |
Chronic cough, defined clinically as a cough that lasts longer than 8 weeks, occurs in 12% of the population and has been associated with significant morbidity globally.[1],[2],[3],[4] Many patients with chronic cough present to their primary care provider, but after initial assessment require additional referrals to secondary or tertiary level care centers.[5] Subsets of patients that require further chronic cough work up tend to have worse symptoms and may incur large financial costs associated with time off from work, transportation to numerous clinic visits, medical visit co-pays, extensive and often fragmented workups, procedures or several pharmacological treatments, and multiple medications.[6],[7] Defining characteristics of chronic cough patients who are referred for the management at the higher level care centers may improve workup and mitigate financial burden.[8]
While risk factors and etiologies of chronic cough have been well characterized in the samples of patients in primary care settings, less is known about the population that have chronic cough requiring referral to higher level care facilities.[8],[9] Study of referred patient populations pose challenges related to geographic variability, differences in primary care provider referral patterns, and lack of standardized referral protocols for chronic cough. However, better understanding of chronic cough patients referred to higher level care facilities may help primary care physicians more readily identify patients requiring referral, promote refinement of existing workup protocols, and identify exposures that could be prevented through community level interventions.[10],[11]
This study aimed to determine the prevalence of various chronic cough etiologies among a cohort of patients with primary complaint of chronic cough, who were evaluated at a single tertiary care center from 2009 to 2020, compare those etiologies to previously published data from primary care settings, and identify key differences that may influence referral algorithms. Additionally, we also aimed to identify socio-demographic correlates of chronic cough etiology among the same cohort of patients that could potentially inform community level interventions or primary care management.
| Methods | | |
Study population
This retrospective study performing patient chart reviews was approved by the Emory Institutional Review Board (IRB#: IRB00054821). Patients seen at Emory Healthcare in Atlanta, Georgia, USA from May 2009 to May 2020 were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th edition code for Cough (R05) from the Emory clinical data warehouse (CDW). CDW is a repository for information collected from various business and clinical operations within the Emory Healthcare system. Data available within CDW includes patient demographics, billing, visits, provider information, diagnoses and procedures, and clinical laboratory results. A data query was run in CDW to include and create a list of patients that had ever been evaluated for primary complaint of chronic cough at Emory; the team of evaluators included pulmonologists, interventional pulmonologists, otolaryngologists, gastroenterologists, speech-language pathologists, allergists, immunologists, and environmental scientists. Patient chart reviews were conducted for the list of patients and subjects aged 18–90 years with a cough lasting > 8 weeks were included in the study.
Outcome
Primary cough etiology was determined as the primary outcome of interest and demographic distribution of the etiologies as secondary outcome. Treatment and procedures performed for all etiologies were evaluated in this study. In some cases, there was no primary cough etiology and those were handled as follows: if the most likely diagnosis changed throughout evaluation or after treatment initiation, then the primary etiology was taken from the most recent note; if there was clear discordance regarding the diagnosis between specialties then the etiology was taken to be multifactorial. Further, if notes specifically documented that the diagnosis was pending further work up, then those participants were categorized as having an incomplete workup. Diagnoses were categorized as follows: multifactorial, gastroesophageal reflux disorder (GERD), neurogenic cough, upper airway structural issues, upper airway cough syndrome or postnasal drip, bronchiolitis or bronchitis, asthma, chronic obstructive pulmonary disease (COPD), chronic infection, bronchiectasis, interstitial lung disease, sarcoidosis, primary or metastatic neoplasms, irritants, angiotensin-converting enzyme (ACE) inhibitors, heart failure, cystic fibrosis, granulomatosis with polyangiitis, pneumothorax, and eosinophilic esophagitis.[12] Categories were based upon common groupings reported in the prior literature and adapted to fit the study sample.[12],[13]
Exposures
Socio-demographic variables included were age at first visit (years), sex (male, female), race (White, Black, Hispanic, Asian, Native American, and Multiracial), zip code, and medical insurance at first visit (public only/any private). Zip codes were intended as a proxy measure for neighborhood-level exposures and socioeconomic status (SES); thus, they were converted to percentage of people living below the poverty line within that zip code according to 2018 census data.[14],[15] Although postal zip code data do not precisely match census zip code tabulation areas, they are a readily available measure useful to identify trends warranting additional investigation.[14],[16]
Duration of chronic cough was categorized into three groups (8 weeks–6 months, 6 months-2 years, and more than 2 years) based on the distribution of the current sample and specificity of data reported in the clinical notes. Participant smoking status was divided as current, former, and never smokers using Center for Disease Control, National Health Interview Survey definition.
Analyses
Analyses were performed using Statistical Analysis System version 9.4. Means and frequency procedures were conducted for the continuous and categorical variables, respectively. The Chi-square test to explore the categorical variables and analysis of variance (ANOVA) tests were used to determine if there were significant differences in socio-demographic characteristics between at least one etiology group compared to all others. In addition to ANOVA, post hoc tukey comparison was used for pairwise comparisons. Etiologies with a sample size of n < 5 and participants with missing data for the relevant analyses were excluded from the statistical analyses. P < 0.05 was considered statistically significant.
| Results | | |
A list of one thousand three hundred and seventy-seven patient records was identified from the Emory CDW. One thousand one hundred and fifty-two met inclusion criteria after review of the patient electronic medical record and were included in the present analyses. The population included 762 (66.1%) female patients, and 759 (65.9%) patients were over 55 years old. The smoking status of the cohort was as follows: 679 (58.9%) were never smokers, 370 (32.1%) were former smokers, and 96 (8.3%) were current smokers. Participants identified predominantly as white (46.5%) or black (42.4%). A total of 3.6% were Asian, 1.5% were Hispanic, and 1.0% were Native American or multiracial. Mean percent poverty within the zip codes participants lived in was 17.8%.Four hundred and three (34.9%) people reported a duration of chronic cough longer than 2 years, 314 (27.2%) had a cough for between 6 months to 2 years, and 349 (30.3%) had a cough for between 8 weeks and 6 months [Table 1]. | Table 1: Demographic characteristics of chronic cough participants evaluated at a tertiary care center (2009-2020)
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The most common etiologies of chronic cough identified in the sample were neurogenic cough (n = 196, 17%), gastroesophageal reflux disease (n = 114, 9.9%), asthma (n = 93, 8.1%), and COPD (n = 80, 6.9%). Neurogenic cough was defined as a chronic hypersensitivity response resulting from laryngeal neuropathy followed by a viral illness or another triggering stimulus; it may also be attributed to hypersensitivity of superior laryngeal nerve(s). This is often a diagnosis of exclusion after ruling out other causes. Two hundred and thirteen (18.5%) patients were reported to have chronic cough caused by multiple underlying etiologies; no clear primary etiology could be established even after multiple evaluations from two or more sub-specialties. Ninety-nine (8.6%) patients were still undergoing further workup at the time of this study, and therefore, a primary etiology was still unknown [Table 2]. | Table 2: Sociodemographic characteristics of participants sorted by primary cough etiology (2009-2020)
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Statistically significant differences between age, sex, and race were found when patients were stratified by primary cough etiology [Table 2]. Based on age, people with sarcoidosis (mean [standard deviation]; 49.6 [13.2]), asthma (56.0 [15.6]), and neurogenic cough (56.3 [13.9]) tended to be younger, while those with COPD tended to be older (66.1 [9.9]). All statistically significant pairwise comparisons are presented in [Table 2] (footnotes). By sex, those with COPD (% female [n], 46.3% [50]), sarcoidosis (47.4% [51]), bronchitis or bronchiolitis (59.5% [50]), and heart failure (50% [54]) were more male-predominant than other etiologies. By race, patients with neurogenic cough (% white [n], 63.3% [48]) and bronchiectasis (58.8% [51]) tended to be white. Sarcoidosis (26.3% [45]), ACE-inhibitor use (22.2% [44]), and neoplasms (35.5% [48]) were etiologies with the lowest percentage of white people.
Although there were statistically significant differences in etiology by insurance type, there was no significant difference between groups in the percentage of people living within a zip code below the poverty line [Table 2]. Those with neurogenic cough (81.1% [30]) were more likely to have private insurance. Participants with primarily pulmonary etiologies lived in zip codes where poverty rates were higher: COPD (% [n]; 19.8 [6.0]), neoplasms (19.5 [5.8]), bronchitis or bronchiolitis (18.9 [8.4]), and chronic infections (18.3 [6.6]).
Duration of cough and smoking status was significantly different by primary cough etiology. Duration of cough tended to be longer among those with bronchiectasis of unspecified etiology (% longer than 2 years duration [n]; 86.7% [35]), interstitial lung disease (81% [40]), multifactorial (75.6% [43]), pending additional workup (73.6% [44]), and neurogenic cough (72.9% [45]). Smoking rates were higher among those with COPD (% ever smoked [n], 97.5 [16]) and neoplasm (68.9 [47]).
Treatment offered to the study participants included proton-pump inhibitors, H1-blockers, inhalers, antispasmodics, antitussives, and corticosteroids [Table 3]. Short-term corticosteroids treatment was offered as an interim treatment until a diagnosis was made. A longer-term regimen was offered for clinically appropriate cases; procedures performed varied by chronic cough etiology. For example, bronchoscopy and plethysmography were used for individuals with pulmonary etiologies. However, laryngoscopy was preferred for individuals with neurogenic, GERD-related, or multifactorial cough etiology [Table 4]. An empirical treatment was used until a diagnosis was established, after which the treatment was directed toward the specific etiology. | Table 3: Treatment provided to the patients stratified by etiology (2009-2020)*
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| Discussion | | |
In this retrospective review of a large sample of patients with chronic cough evaluated at least once at a tertiary care center, the most common etiology was neurogenic cough. In the male population COPD, sarcoidosis, bronchitis or bronchiolitis, and heart failure was more prominent than thefemale cohort. In addition, pulmonary etiologies were more prevalent in zipcodes with high poverty rate. Differences in sex and SES by cough etiology may help primary care physicians identify etiology-specific risk factors and referral to appropriate chronic cough specialists.
Neurogenic cough was the single most common underlying diagnosis. These findings contradict previous research suggesting upper airway cough syndrome, asthma, COPD, GERD, and nonasthmatic eosinophilic bronchitis are more common etiologies.[12],[13] Discrepancies may be related to the patient population: while participants in this study were identified at a tertiary care center, other investigations took place within primary care or pulmonology clinics.[17],[18],[19],[20],[21] Patients referred to tertiary care centers receive more thorough workup, other diagnoses could be excluded to diagnose neurogenic cough.[22] Prior research in primary care settings also suggests that 7%–40% of patients complaining of persistent cough had no identifiable etiology and were presumed to have neurogenic cough.[23] Early referral to otolaryngologists for a trial of neurogenic cough therapies, rather than waiting until all other avenues have been exhausted, may reduce symptom burden.
Among prior studies of chronic cough in specialty clinics, patients are predominantly female; this finding is reflected in the current study too.[24] Such a trend may partly be explained by the fact that patients with neurogenic cough are mostly female.[25],[26] In addition, no significant differences between etiologies of chronic cough and SES, as measured by proportion of people living below the poverty line within the participant's zip code, were noted. Neighborhood poverty rates among participants (17.8%) were comparable to metro Atlanta (20.8%) but higher than poverty rates for Georgia (13.3%) and nationally (12.3%).[27] As such, area-level SES among the study sample may not be generalizable beyond urban Atlanta. Although not statistically significant, participants with neoplasms and COPD tended to live in zip codes with higher poverty rates, consistent with prior research that links SES with environmental exposures that contribute to cough, COPD, and neoplasms.[28],[29],[30],[31] Among patients from low SES areas, primary care physicians should carefully screen for environmental exposures and may require a low threshold for pulmonology referrals. Several treatment options were provided to the patients, which varied significantly by the cough etiology. Similarly, various procedures performed were dependent upon the cough origin. Therefore, the evaluation of cough causation is of utmost importance by a group of specialists in gastroenterology, pulmonology and laryngology.
Many study participants had a cough lasting longer than 2 years or still had ongoing workup, emphasizing the need for more streamlined workup for chronic cough patients. One way to mitigate these challenges would be through a probability-based algorithm, where clinical probability of disease governs the need for medical workup, which may identify the etiology of cough in 93% of cases.[32] In addition, widespread adoption of multidisciplinary cough clinics with providers from medical and rehabilitative specialties could ease the burden on primary care physicians regarding referral decisions to cough specialists. Further, multidisciplinary cough clinics could offer a more streamlined and comprehensive workup and treatment plan.[33] Emory Healthcare, after the end date of this study, has recently implemented a multidisciplinary cough clinic including pulmonologists, interventional pulmonologists, otolaryngologists, gastroenterologists, speech-language pathologists, allergists, immunologists, and environmental scientists; patients attend one clinic visit staffed simultaneously by these clinical providers. Understanding how multidisciplinary clinics influence chronic cough diagnosis, duration, and disease burden may ultimately improve the care of patients with chronic cough.
This was a single-site study and generalizability to other settings may be limited. Referral patterns may have been influenced by local primary care provider preferences, seasonal changes, geographic prevalence of diseases, and the availability of tertiary care centers in the region. Although the current study has limited external validity, future studies in other tertiary care settings can be compared to the present study to tease out regional differences and further inform referral protocols. In addition, eligible participants may have been missed due to errors in International Classification of Diseases-10 coding, and some may have been lost to follow-up prior to diagnosis.[34] Among the included participants, there was no systematic method to verify chronic cough etiology, and the specialty of the diagnosing provider likely biased final diagnoses. Finally, although proportion of people living below the poverty line in participant zip codes is a previously used surrogate for neighborhood level SES, other neighborhood level SES indices requiring data not available in this study have been shown to be more reliable.[35]
| Conclusion | | |
In conclusion, we found that patients with chronic cough seen at a single multidisciplinary tertiary care clinic had diverse cough etiologies that varied based on key demographic variables. Neurogenic cough was the most prevalent primary etiology and early referral to otolaryngologists for chronic cough may be beneficial. Future studies should evaluate how socio-demographic factors influence the etiology of chronic cough through prospective observational studies and examine the efficacy of multidisciplinary cough clinics in diagnosing and treating chronic cough patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]
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