Cough Sensitivity to Several External Triggers is Associated with Multiple Non-respiratory Symptoms.

PURPOSE: Enhanced responsiveness to external triggers is thought to reflect hypersensitivity of the cough reflex. It may involve an enhanced sensitivity of the afferent nerves in the airways and/or an abnormal processing of the afferent information by the central nervous system (CNS). The CNS processing of cough has been shown to involve the same regions as those in symptom amplification, a phenomenon that often manifests as multiple symptoms. The main purpose of the present study was to define whether the presence of several cough triggers is associated with multiple symptoms. METHODS: 2131 subjects with current cough responding to two email surveys filled in a comprehensive questionnaire about social background, lifestyle, general health, doctors' diagnoses and visits, symptoms, and medication. Multiple symptoms was defined as three or more non-respiratory, non-mental symptoms. RESULTS: A carefully controlled multiple regression analysis revealed that the number of cough triggers was the only cough characteristic associating with multiple non-respiratory, non-mental symptoms [aOR 1.15 (1.12-1.19) per one trigger, p < 0.001]. Among the 268 subjects with current cough both in the first survey and in the follow-up survey 12 months later, the repeatability of the trigger sum was good with an intraclass correlation coefficient of 0.80 (0.75-0.84). CONCLUSION: The association between the number of the cough triggers and multiple symptoms suggests that the CNS component of cough hypersensitivity may be a manifestation of non-specific alteration in the CNS interpretation of various body sensations. The number of cough triggers is a repeatable measure of cough sensitivity.

Characteristics of idiopathic pulmonary fibrosis -associated cough. a case-control study.

BACKGROUND: Most patients with idiopathic pulmonary fibrosis (IPF) complain of cough. IPF-associated cough is widely characterized as dry or non-productive. The aim of this study was to compare chronic cough in early stage IPF patients to cough in subjects with chronic cough from a community-based sample and, especially, to investigate whether cough in IPF is less productive than chronic cough in a community-based sample. METHODS: The IPF cough population consisted of 46 biopsy-confirmed patients who complained of chronic cough. Control population consisted of subjects with chronic cough, gathered by a community-based email survey sent to public service employees and the Finnish Pensioners' Federation. A case-control setting was applied by having four age, gender, and smoking-status matched subjects from the community sample for each IPF cough patient. A cough specific quality of life questionnaire (Leicester Cough Questionnaire (LCQ)) was filled in by all subjects. The LCQ questionnaire contains 19 questions, each question is scored from 1 to 7 and total score from 3 to 21 with a smaller value indicating more severe impairment. RESULTS: The sputum production frequency, as assessed by LCQ question 2, was 5.0 (3.0-6.0) in the IPF chronic cough population and 5.0 (3.0-6.0) in the community-based chronic cough population (median and interquartile range p= 0.72). The LCQ total score was 14.8 (11.5-18.1) in the IPF chronic cough population and 15.4 (13.0-17.5) in the community-based chronic cough population (p=0.76). The domain impact scores were physical, 4.9 (3.9-6.1) vs. 5.1 (4.5-5.6) (p=0.80); psychological, 4.6 (3.7-5.9) vs. 4.7 (3.9-5.7) (p=0.90); and social, 5.5 (3.7-6.5) vs. 5.5 (4.5-6.3) (p=0.84), respectively. Furthermore, cough response to paint or fumes, cough disturbing sleep, and cough frequency per day did not differ between the groups. CONCLUSION: Cough in early stage IPF patients was not distinguishable from chronic cough in the community-based population by LCQ. Especially, there was no difference in the self-reported frequency of cough-associated sputum production.

Deep Inspiration-Provoked Cough: A Sign of Cough Reflex Arc Hypersensitivity.

Deep inspiration-provoked cough (DIPC) is a form of allotussia. Allotussia is thought to be a manifestation of cough reflex arc hypersensitivity but objective evidence about this is lacking. 36 subjects with chronic cough and 25 healthy subjects underwent mannitol and citric acid cough provocation tests. DIPC was defined as two or more coughs after deep inhalation of an empty mannitol capsule. Citric acid was administered utilizing a dosimetric nebulizer during controlled tidal breathing. Nine subjects demonstrated DIPC, 8/36 subjects with chronic cough and 1/25 healthy subjects (p = 0.048). The concentration of citric acid to provoke five or more coughs (C5) was 23.4 (63.8) mM among subjects with DIPC and 750 (2941) mM among the subjects without it (p = 0.006). The number of deep inspiration-provoked coughs correlated with the citric acid C5 (Rs -0.38, p = 0.002). In conclusion, DIPC, a form of allotussia, is associated with cough reflex arc hypersensitivity.Trial Registration Number.ClinicalTrials.gov database KUH5801136.

Cluster analysis in 975 patients with current cough identifies a phenotype with several cough triggers, many background disorders, and low quality of life.

BACKGROUND: Recognition of disorder phenotypes may help to estimate prognosis and to guide the clinical management. Current cough management guidelines classify patients according to the duration of the cough episode. However, this classification is not based on phenotype analyses. The present study aimed to identify cough phenotypes by clustering. METHODS: An email survey among employed, working-age subjects identified 975 patients with current cough. All filled in a comprehensive 80-item questionnaire including the Leicester Cough Questionnaire. Phenotypes were identified utilizing K-means partitional clustering. A subgroup filled in a follow-up questionnaire 12 months later to investigate the possible differences in the prognosis between the phenotypes. RESULTS: Two clusters were found. The cluster A included 608 patients (62.4% of the population) and the cluster B 367 patients (37.6%). The three most important variables to separate the clusters were the number of the triggers of cough (mean 2.63 (SD 2.22) vs. 6.95 (2.30), respectively, p < 0.001), the number of the cough background disorders (chronic rhinosinusitis, current asthma, gastroesophageal reflux disease, 0.29 (0.50) vs. 1.28 (0.75), respectively, p < 0.001), and the Leicester Cough Questionnaire physical domain (5.33 (0.76) vs. 4.25 (0.84), respectively, p < 0.001). There were significant interrelationships between these three variables (each p < 0.001). Duration of the episode was not among the most important variables to separate the clusters. At 12 months, 27.0% of the patients of the cluster A and 46.1% of the patients of the cluster B suffered from cough that had continued without interruptions from the first survey (p < 0.001). CONCLUSIONS: Two cough phenotypes could be identified. Cluster A represents phenotype A, which includes the majority of patients and has a tendency to heal by itself. The authors propose that cluster B represents phenotype TBQ (Triggers, Background disorders, Quality of life impairment). Given the poor prognosis of this phenotype, it urges a prompt and comprehensive clinical evaluation regardless of the duration of the cough episode.

Long-term prognosis of chronic cough: a prospective, observational cohort study.

BACKGROUND: The long-term prognosis of chronic cough and its determinants need to be clarified. METHODS: This is a prospective, observational cohort study. Eighty-nine unselected subjects with chronic (> 8 weeks' duration) cough were carefully investigated: Clinical examination, symptom questionnaire, Leicester Cough Questionnaire (LCQ), skin prick tests, ambulatory peak expiratory flow monitoring, spirometry before and after 0.4 mgs of salbutamol, exhaled nitric oxide concentration measurement, hypertonic saline cough provocation test, and histamine bronchial provocation test. After five years, a letter was sent to the subjects containing questions about continuation of cough, smoking, indoor exposures, presence of co-morbidities, and current medication. It also contained LCQ and Cough Clinic diagnostic questionnaire. Sixty-eight subjects (76%) responded. RESULTS: At five years, continuing regular cough was present in 31 (46%) of the subjects and continuing impairment in cough-related quality of life (less than 1.3 points' improvement in LCQ) in 32 (47%). Continuing regular cough was associated with presence of chronic rhinitis or esophageal reflux disease, baseline mild airway responsiveness to histamine, and baseline strong cough responsiveness to hypertonic saline. Continuing impairment in cough-related quality of life was associated with high body mass index, absence of atopy, absence of pets, and high number of background disorders (esophageal reflux disease, asthma, or chronic rhinitis). CONCLUSIONS: Almost half of subjects with chronic cough suffered of the disorder at five years from initial assessment. Several possible determinants of poor prognosis could be identified.

Prevalence and determinants of hyperglycaemia in pneumonia patients.

BACKGROUND: Hyperglycaemia during pneumonia prolongs the hospitalization and increases the risks of complications and death. However, its prevalence and determinants have not been systematically assessed. METHODS: This was a prospective, cross-sectional study. The material consisted of 153 hospitalized patients with pneumonia. Patients needing intensive care unit treatment were excluded. The height, weight, waist circumference, oxygen saturation, blood pressure, temperature, heart rate, and Karnofsky score were measured at admission. Blood tests included glycosylated haemoglobin A1c (gHbA1c), C-reactive protein (CRP), leukocytes, urea, and arterial blood gas analysis. Plasma glucose was measured 7 times during the first day on the ward. Hyperglycaemia was defined as a fasting glucose > 7.0 mmol/l or postprandial glucose > 11.1 mmol/l. RESULTS: Ninety-two patients (60%) showed hyperglycaemia. Twenty-two patients had a diagnosis of diabetes before hospitalization. Of the 131 patients without such a diagnosis, 72 (55%) showed hyperglycaemia. Of these, 67 showed fasting hyperglycaemia and 36 postprandial hyperglycaemia. In the binary logistic regression analysis, the following factors showed independent associations with the presence of hyperglycaemia: advanced age, high gHbA1c, high CRP, and high blood leukocyte level. CONCLUSIONS: More than half of non-diabetic patients with mild to moderate pneumonia demonstrated hyperglycaemia. The main determinants of hyperglycaemia were an abnormal pre-pneumonia glucose metabolism and the intensity of the pneumonic inflammation. Systematic screening of hyperglycaemia in all hospitalized pneumonia patients appears reasonable to identify high-risk patients.

Inflammatory myositis-associated interstitial lung disease can be distinguished from that associated with other connective tissue diseases.

Background: Acute onset of interstitial lung disease (ILD) has been described in patients with idiopathic inflammatory myositis (IIM), but controlled studies about this issue are sparse. The aim of this study was to compare disease onset, demographics, and high-resolution computed tomography (HRCT) patterns in IIM-ILD and other connective tissue disease (CTD)-ILDs. Methods: Clinical and radiological data of 22 IIM-ILD and 132 other CTD-ILD patients was retrospectively gathered from hospital registries between January 2000 and November 2019. Data was re-assessed and compared using a multivariate analysis. Results: Compared to other CTD-ILDs, the patients with IIM-ILD were younger (59.7 vs. 68.0 years, P=0.023), more often non-smokers (71.4% vs. 45.7%, P=0.029) and displayed radiological nonspecific interstitial pneumonia/organizing pneumonia (NSIP/OP) overlap pattern more frequently (27.3% vs. 1.5%, P<0.001). The onset of ILD was acute with patients needing intensive care significantly more often in IIM-ILD than in other CTD-ILDs (22.7% vs. 2.3%, P<0.001). In most patients ILD was diagnosed before or simultaneously with IIM presentation unlike in other CTD-ILDs (90.9% vs. 47.7%, P<0.001). In multivariate analysis, NSIP/OP overlap pattern, acute onset disease treated in intensive care unit and ILD preceding or being diagnosed simultaneously with CTD were significantly associated with IIM-ILD. The multivariate model, supplemented with age, had excellent diagnostic performance identifying IIM-ILD [area under curve (AUC) 0.845]. Conclusions: Unlike other CTD-ILDs, IIM-ILD often develops acutely, simultaneously with the systemic disease. Therefore, clinicians should consider IIM-ILD as an option of differential diagnosis in patients with acute ILD and promptly test muscle enzymes as well as comprehensive autoantibody tests.

Daily Inhaled Corticosteroids Treatment Abolishes Airway Hyperresponsiveness to Mannitol in Defence and Police Recruits.

Background: Airway hyperresponsiveness (AHR) is a key pathophysiological feature of asthma and causes exercise-induced bronchoconstriction (EIB). Indirect bronchial provocation tests (BPTs) (e.g., exercise, mannitol) aid to diagnose asthma and identify EIB. Daily inhaled corticosteroids (ICS) can abolish AHR caused by indirect stimuli. Where strenuous physical exertion is integral to an occupation, identification of those at risk of EIB is important and documentation of inhibition of AHR with ICS is required before recruitment. Methods/Objectives: A retrospective analysis was performed on 155 potential recruits with AHR to mannitol who underwent follow-up assessment after daily ICS treatment to determine the proportion that can abolish AHR using ICS and to determine any predictors of the persistence of AHR. Results: Airway hyperresponsiveness was abolished in the majority (84%, n = 130) over the treatment period (mean ± SD 143 ± 72days), and it was defined as the provoking dose of mannitol to cause a 15% fall in FEV1 (cumulative inhaled dose of mannitol to cause 15% fall in FEV1, PD15) improved from (GeoMean) 183 to 521 mg. Compared with recruits in whom AHR was abolished with daily ICS (i.e., no 15% fall in FEV1 to the maximum cumulative dose of mannitol of 635 mg), in those where AHR remained (16%, n = 25), baseline AHR was more severe (PD15: 85 mg vs. 213 mg, P < 0.001), baseline FEV1% was lower (89 vs. 96%; 95%CI:2-12, P=0.004), and they had a longer follow-up duration (180 vs. 136 days; 13-74, P = 0.006). Baseline FEV1% (adjusted odds ratio 0.85; 95%CI:0.77-0.93), FEV1/FVC (0.78; 0.67-0.90), FEF25-75% (1.15; 1.06-1.25), and airway reactivity to mannitol (%Fall/cumulative dose of mannitol multiplied by 100) (1.07; 1.03-1.11) predicted AHR remaining after daily ICS. Conclusion: Airway hyperresponsiveness to mannitol can be abolished after 20 weeks of daily treatment with ICS. Inhibition of AHR is likely due to attenuation of airway inflammation in response to ICS treatment. Increased airway reactivity and lower spirometry variables predicted the persistence of AHR. Thus, those with a slower response to daily ICS on AHR can potentially be identified at the commencement of monitoring ICS using inhaled mannitol.

Validation of the cough phenotype TBQ among elderly Finnish subjects.

Background: Phenotypes can be utilised in the clinical management of disorders. Approaches to phenotype disorders have evolved from subjective expert opinion to data-driven methodologies. A previous cluster analysis among working-age subjects with cough revealed a phenotype TBQ (triggers, background disorders, quality-of-life impairment), which included 38% of the subjects with cough. The present study was carried out to validate this phenotyping among elderly, retired subjects with cough. Methods: This was an observational cross-sectional study conducted via email among the members of the Finnish Pensioners' Federation (n=26 205, 23.6% responded). The analysis included 1109 subjects with current cough (mean±sd age 72.9±5.3 years; 67.7% female). All filled in a comprehensive 86-item questionnaire including the Leicester Cough Questionnaire. Phenotypes were identified utilising k-means partitional clustering. Results: Two clusters were identified. Cluster A included 75.2% of the subjects and cluster B 24.8% of the subjects. The three most important variables to separate the clusters were the number of cough triggers (mean±sd 2.47±2.34 versus 7.08±3.16, respectively; p<0.001), Leicester Cough Questionnaire physical domain (5.38±0.68 versus 4.21±0.81, respectively; p<0.001) and the number of cough background disorders (0.82±0.78 versus 1.99±0.89 respectively; p<0.001). Conclusion: The phenotype TBQ could be identified also among elderly, retired subjects with cough, thus validating the previous phenotyping among working-age subjects. The main underlying pathophysiological feature separating the phenotype TBQ from the common cough phenotype is probably hypersensitivity of the cough reflex arc.

Sputum production in chronic cough increases the probability of asthma: a cross-sectional questionnaire study.

Sputum production may suggest asthma as the most probable background disorder maintaining the cough https://bit.ly/2Qk8aar.

Persistence of chronic cough in a community-based population.

Chronic cough causes significant impairment in the quality of life and is often immune to treatment. Previous studies about its persistence have focused on patients managed in special cough clinics. Little is known about the persistence of chronic cough in unselected populations. In this prospective follow-up study, we investigated factors that predict the persistence of cough at 12-month follow-up in a community-based study of subjects with chronic cough. The first e-mail survey in 2017 included a questionnaire about current cough and its risk factors. The 264 subjects who reported chronic cough were sent a follow-up questionnaire 12 months later. The response rate was 77.7% (205 subjects), of whom 165 subjects (80.5%) still had cough in 2018. In multivariate analysis, the following baseline factors predicted the persistence of cough at 12 months; gastro-oesophageal reflux disease (adjusted OR (aOR) 5.02 (95% CI 1.10-22.83)), presence of a chemical trigger (aOR 2.88 (95% CI (1.20-7.00)), duration of cough more than 1 year (aOR 2.80 (95% CI 1.27-6.22)), frequent somatic symptoms (aOR 1.31 (95% CI 1.07-1.59)), and low number of family members (aOR 0.71 (95% CI 0.52-0.98)). In conclusion, most patients with chronic cough still suffer from cough 1 year later. The presence of gastro-oesophageal reflux disease is the main predictor for the persistence of cough.

Cough-provocation tests with hypertonic aerosols.

Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

Cough as an adverse effect on inhalation pharmaceutical products.

Cough is an adverse effect that may hinder the delivery of drugs into the lungs. Chemical or mechanical stimulants activate the transient receptor potential in some airway afferent nerves (C-fibres or A-fibres) to trigger cough. Types of inhaler device and drug, dose, excipients and formulation characteristics, including pH, tonicity, aerosol output and particle size may trigger cough by stimulating the cough receptors. Release of inflammatory mediators may increase the sensitivity of the cough receptors to stimulants. The cough-provoking effect of aerosols is enhanced by bronchoconstriction in diseased airways and reduces drug deposition in the target pulmonary regions. In this article, we review the factors by which inhalation products may cause cough.

[Long term oxygen therapy: many hopes, little proof]. / Pitkäaikainen happihoito: paljon toiveita, vähän näyttöjä.

Long-term oxygen therapy extends the life span of hypoxemic patients with chronic obstructive pulmonary disease (COPD). The patients often have great expectations concerning the quality of life, but oxygen therapy does neither relieve dyspnea nor reduce the need for hospital treatments. Oxygen therapy in diseases other than COPD lacks scientific basis. It is worthwhile to start in-hospital oxygen therapy by determining the oxygen flow with a device given to the patient, and the effect of the therapy on the nocturnal accumulation of carbon dioxide is checked. In the future, focus should be on other forms of therapy, such as rehabilitation.

Predictors of prolongation in recent-onset cough.

Chronic cough greatly decreases the quality of life and is often refractory to treatment. Interventions at an early stage could prevent cough from becoming chronic. To this end, the patients at high risk of cough prolongation would need to be identified. In this study, we investigated the factors that predicted cough at 12 months among subjects with a recent-onset cough. This was a prospective, observational follow-up study in a community-based population consisting of working-age subjects. The first e-mail survey in 2017 included a comprehensive questionnaire about current cough and its risk factors. The 259 subjects who reported a recent-onset (<8 weeks) cough were sent a follow-up questionnaire 12 months later. The response rate was 72.6% (188 subjects). There were 99 subjects (52.7%) with cough in 2018. The following baseline factors predicted the presence of any cough at 12 months in the multivariable analysis: wheezing (adjusted odds ratio (aOR 2.80, 95% CI 1.3-5.27), dog ownership (aOR 2.56, 95% CI 1.21-5.44), cough duration >3 weeks (aOR 2.29, 95% CI 1.11-4.76), family history of chronic cough (aOR 2.20, 95% CI 1.13-4.30), body mass index >25 kg·m-2 (aOR 2.06, 95% CI 1.02-4.15) and frequent somatic symptoms (aOR 1.36, 95% CI 1.13--1.64). There were 29 subjects (15.4%) with continuous cough and 66 subjects (35.1%) with recurrent cough. The risk factors were completely different between recurrent and continuous cough. It may be possible to identify the risk factors of cough prolongation among subjects with recent-onset cough. Early interventions should be targeted to these kinds of patients.

Subfreezing air as a cough trigger and multiple triggers are strongly associated with the presence of asthma in chronic cough.

BACKGROUND: Management of chronic cough relies on the recognition of cough background disorders. It is not known whether certain cough triggers are associated with specific background disorders. METHODS: This was an e-mail study to public service employees of two towns in Finland. The questionnaire included twelve triggers. Current asthma was defined as doctor's diagnosis of asthma and current wheezing. Chronic rhinosinusitis was defined as either nasal blockage or nasal discharge and either facial pain/pressure or reduction/loss of smell for more than three months. Gastroesophageal reflux disease was defined as heartburn and/or regurgitation on at least one day a week during the last three months. Idiopathic cough was defined as absence of any of them. RESULTS: There were 421 subjects with current cough that had lasted at least eight weeks. Subfreezing air as a cough trigger was associated with an adjusted odds ratio (aOR) of 7.27 (4.09-12.9), (p < 0.001), for current asthma. The number of cough triggers was largest in asthma, followed by chronic rhinosinusitis, gastroesophageal reflux, and idiopathic cough (7.05 (6.14-7.96), 4.94 (4.35-5.54), 4.60 (3.77-5.43), and 3.44 (3.02-3.86), respectively, p < 0.001). Presence of five or more triggers was associated with an aOR of 7.49 (3.96-14.2), (p < 0.001) for current asthma. Absence of any cough triggers increased the probability of idiopathic cough (aOR 2.71 (1.54-4.77), p = 0.001). CONCLUSIONS: Subfreezing air as a cough trigger and multiple triggers are strongly associated with the presence of current asthma in chronic cough. Absence of any cough triggers increases the probability of idiopathic cough.

Risk factors for repetitive doctor's consultations due to cough: a cross-sectional study in a Finnish employed population.

OBJECTIVES: Cough is the most common symptom prompting people to consult a doctor, thus representing a huge cost to the healthcare. This burden could be reduced by decreasing the number of repetitive consultations by the same individuals. Therefore, it would be valuable to recognise the factors that associate with repetitive doctor's consultations due to cough. DESIGN: A cross-sectional, email survey. SETTING: Public service employees in two Finnish towns. PARTICIPANTS: The questionnaire was sent to 13 980 subjects; 3695 (26.4 %) participated. INTERVENTIONS: The questionnaire sought detailed information about participant characteristics, all disorders diagnosed by a doctor, various symptoms and doctor's consultations. Those with current cough were inquired about cough characteristics and filled in the Leicester Cough Questionnaire (LCQ). PRIMARY OUTCOME: Repetitive (≥3) doctor's consultations due to cough during the previous 12 months. RESULTS: There were 205 participants (5.5% of the participants) with repetitive consultations. They accounted for 848 out of the 1681 doctor's consultations (50.4%) due to cough. Among all participants, repetitive consultations were mainly related to the presence of asthma (adjusted OR (aOR) 2.90 (2.01 to 4.19)) and chronic rhinosinusitis (aOR 2.40 (1.74 to 3.32)). Among the 975 participants with current cough, repetitive consultations were mainly related to a low LCQ total score (aOR 3.84 (2.76 to 5.34) per tertile). Comorbidity, depressive symptoms and smoking were also associated with repetitive consultations. CONCLUSIONS: A modest proportion of subjects with repetitive consultations is responsible for every second doctor's consultation due to cough. The typical features of these subjects could be identified. These findings can help to focus on certain subpopulations in order to plan interventions to reduce the healthcare burden attributable to cough.

Comparison of mannitol and citric acid cough provocation tests.

RATIONALE: Citric acid has been used as a cough provocation test for decades. However, the methods of administration have not been standardized. Inhaled mannitol is a novel cough provocation test, which has regulatory approval and can be performed utilizing a simple disposable inhaler in a standardized manner. OBJECTIVE: To compare the mannitol and citric acid cough provocation tests with respect to their ability to identify subjects with chronic cough and their tolerability. METHODS: Subjects with chronic cough (n = 36) and controls (n = 25) performed provocation tests with mannitol and citric acid. Both tests were video recorded. Cough sensitivity was expressed as coughs-to-dose ratios (CDR) and the cumulative doses to mannitol or concentration to citric acid evoking 5 coughs (C5). Forced expiratory volume in 1 s (FEV1), visual analogue scales (VAS), test completion rates and the total cough frequencies were analysed. RESULTS: Mannitol and citric acid CDR both effectively separated those with cough and the control subjects (AUC 0.847 and 0.803, respectively) as did C5 (AUC 0.823 and 0.763, respectively). There was a good correlation between the cough sensitivity provoked by the two stimuli, either expressed as CDR (r = 0.65, p < 0.001) or C5 (r = 0.53, p = 0.001). Both tests were similarly tolerated in terms of VAS, although more patients discontinued the mannitol test early, primarily due to cough. CONCLUSIONS: Mannitol and citric acid tests correlated well, equally identified subjects with chronic cough and their tolerability was similar. The feasibility issues, strict standardisation and regulatory approval may favour mannitol to be used in clinical cough research.

Defining the risk factors for acute, subacute and chronic cough: a cross-sectional study in a Finnish adult employee population.

OBJECTIVES: Chronic cough is linked to various long-standing risk factors like asthma, chronic rhinitis and oesophageal reflux disease. On the contrary, acute and subacute cough are usually considered to be caused by acute respiratory infections. Little is known about the possible long-standing risk factors for acute and subacute cough. In this study, we have identified the long-standing risk factors for acute, subacute and chronic cough in order to identify the risk factors specifically associated with chronic cough. DESIGN: A comprehensive 80-item questionnaire was sent via email to the participants. SETTING: A community-based study to all public service employees of two towns in central Finland. PARTICIPANTS: There were 13 980 employees, of them 3697 responded (26.4%). Among the responders, there were 199 subjects with current daily acute cough (duration <3 weeks, prevalence 5.4%), 126 subjects with current daily subacute cough (duration 3-8 weeks, prevalence 3.4%) and 267 subjects with current daily chronic cough (duration >8 weeks, prevalence 7.2%). PRIMARY OUTCOME MEASURES: The risk factors that associated with each cough subtype. The subjects without any cough formed the reference group. RESULTS: Several risk factors were associated with both short and long cough subtypes namely family history of chronic cough, moisture damage exposure and number of reported somatic symptoms. Furthermore, allergy was associated with acute and subacute cough. Current asthma and chronic rhinitis were associated with subacute and chronic cough. Oesophageal reflux disease and advanced age were associated with chronic cough. CONCLUSIONS: The specific risk factors for chronic cough were oesophageal reflux disease and advanced age. Acute and subacute cough should not be regarded merely as symptoms of acute respiratory infections but possible manifestations of long-standing risk factors. A new risk factor for all cough types was family history of chronic cough.