Extrathoracic Airway Hyperresponsiveness Research Articles

Przewlekły kaszel w praktyce otorynolaryngologicznej

Cough is the most common symptom of the upper and lower airway diseases. In its nature, cough is a defence reflex mechanism of the respiratory tract that is used to clear the upper airways. Persistent cough is associated with a whole range of conditions, both respiratory and non-respiratory disorders. Chronic cough, defined as cough lasting for more than 8 weeks, is reported by 3–40% if the general population and has an important impact on patients' quality of life. In non-smokers upper airways cough syndrome, previously referred to as post nasal drip syndrome is one of the most common causes of chronic cough with asthma and gastroesophageal reflux. Chronic cough in majority of cases is related to more than one disease. The pathogenesis of cough from UACS remains unclear, but some authors indicate, that extrathoracic airway hyperresponsiveness – EAHR could be the responible mechanism. Chronic cough can present difficulties in diagnosis and management. Otorhinolaryngological assessment seems to be necessary component of diagnostic proccess, particularly in non-smoking, not-treated with ACEinhibitors adults with normal chest radiogram and excluded lower airways pathology. ENT approach in chronic cough could based on: ENT medical history and ENT examination, sinus CT scans, videolaryngoscopy, acoustic rhinometry, rhinomanometry, nasal cytology and nasal-sinus endoscopy. Such complex diagnostic tools, included otorhinolaryngological procedures, in many cases are necessary to recognized the cause of chronic cough and to establishe the accurate diagnosis, which implies a higher chance to effective treatment.

Characterization of laryngeal dysfunction in chronic persistent cough

Laryngeal symptoms are increasingly recognized to occur in chronic persistent cough and may result from the sensory hyperresponsiveness that characterizes this condition. Apart from cough, the motor consequences of sensory activation have not been well described in chronic persistent cough. The efficacy of speech pathology treatment for chronic cough suggests that laryngeal dysfunction may be relevant in chronic persistent cough. This study investigated the relationship between cough reflex sensitivity and laryngeal dysfunction, which was assessed as paradoxical vocal cord movement (PVCM) and extrathoracic airway hyperresponsiveness, in patients with chronic cough. Cross-sectional case-control comparison of subjects with chronic cough and healthy controls. Adults with chronic persistent cough (n = 25) and healthy controls (n = 11) were assessed by cough-specific quality of life questionnaire, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity, and fibreoptic laryngoscopy to assess PVCM. Laryngeal dysfunction was present in many patients with chronic persistent cough. PVCM was present in 56% of subjects with chronic cough and accompanied by cough reflex hypersensitivity and impaired quality of life. Inspiratory airflows were reduced in cough with PVCM, and there was significant extrathoracic airway hyperresponsiveness. Laryngeal dysfunction is common in chronic cough, where it is manifest as paradoxical vocal cord movement and extrathoracic airway hyperresponsiveness. Laryngeal dysfunction in chronic cough is associated with reduced quality of life. Laryngeal hypersensitivity may be a common mechanism that can be effectively treated by speech language therapy.

Chronic cough and laryngeal dysfunction improve with specific treatment of cough and paradoxical vocal fold movement

RationaleChronic persistent cough can be associated with laryngeal dysfunction that leads to symptoms such as dysphonia, sensory hyperresponsiveness to capsaicin, and motor dysfunction with paradoxical vocal fold movement and variable extrathoracic airflow obstruction (reduced inspiratory airflow). Successful therapy of chronic persistent cough improves symptoms and sensory hyperresponsiveness. The effects of treatment for chronic cough on laryngeal dysfunction are not known.ObjectiveThe aim of this study was to investigate effects of therapy for chronic cough and paradoxical vocal fold movement.MethodsAdults with chronic cough (n = 24) were assessed before and after treatment for chronic persistent cough by measuring quality of life, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity and fibreoptic laryngoscopy to observe paradoxical vocal fold movement. Subjects with chronic cough were classified into those with (n = 14) or without (n = 10) paradoxical vocal fold movement based on direct observation at laryngoscopy.ResultsFollowing treatment there was a significant improvement in cough related quality of life and cough reflex sensitivity in both groups. Subjects with chronic cough and paradoxical vocal fold movement also had additional improvements in extrathoracic airway hyperresponsiveness and paradoxical vocal fold movement. The degree of improvement in cough reflex sensitivity correlated with the improvement in extrathoracic airway hyperresponsiveness.ConclusionLaryngeal dysfunction is common in chronic persistent cough, where it is manifest as paradoxical vocal fold movement and extrathoracic airway hyperresponsiveness. Successful treatment for chronic persistent cough leads to improvements in these features of laryngeal dysfunction.

Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma

Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine - MCh) or indirect (adenosine 5'-monophosphate - AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). We designed a randomized, single-blind, cross-over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV(1)) value (PD(20)MCh); (ii) a provocative dose producing a 25% fall in the maximal mid-inspiratory flow (FIF(50)) from baseline (PD(25)MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV(1) value (PC(20)AMP) and (iv) a provocative concentration producing a 25% fall in the FIF(50) from baseline (PC(25)AMP) for AMP. All 113 patients with CVA responded to PD(20)MCh and 96% and 69% responded to PC(20)AMP, if we used PC(20) </= 200 mg/ml or PC(20) </= 100 mg/ml, respectively, with an excellent correlation between these two tests (r = 0.87 and 0.76, respectively). Extrathoracic AHR associated with AHR was found in 10% in MCh challenge and in 11% with AMP challenge and no patients had EAHR alone. Adenosine challenges correlate well with MCh in patients with CVA. A minority (c. 10%) of CVA patients have EAHR as measured by these tests, while most had AHR as assessed with each of the challenge agents.

Extrathoracic airway hyperresponsiveness as a mechanism of post infectious cough: case report

Post-infectious cough is a common diagnosis in people with chronic cough. However, the specific infectious aetiology and cough mechanisms are seldom identified.We report a case of chronic cough after Mycoplasma pneumoniae lower respiratory tract infection with extrathoracic airway hyperresponsiveness as the cough mechanism. Extrathoracic airway hyperresponsiveness may be a common mechanism in post-infectious cough which may be useful both diagnostically and therapeutically since chronic cough with extrathoracic airway hyperresponsiveness responds to speech pathology treatment.

The role of sensory dysfunction in the development of voice disorders, chronic cough and paradoxical vocal fold movement

Sensory function may be important in the pathogenesis of Chronic Cough (CC) and Paradoxical Vocal Fold Movement (PVFM). This paper aims to explore sensory issues related to the pathogenesis, classification, assessment and management of these conditions. Sensory disruption of the vagus nerve can occur through neural plasticity whereby a change occurs in the way a central neuron reacts to an incoming stimulus. Such disruption can be demonstrated through assessment of cough reflex sensitivity and extrathoracic airway hyperresponsiveness both of which may be increased in CC and PVFM. In addition, sensory function may be determined by measuring the laryngeal adductor reflex, however this phenomenon is yet to be explored in CC and PVFM. The similarity in sensory dysfunction between CC and PVFM provides support for a link between the two conditions. There are also similarities in underlying medical conditions and symptom profiles between CC/PVFM and voice disorders such as muscle tension dysphonia. Although coughing and throat clearing may be contributing factors in the development and maintenance of voice disorders, they may occur in response to extrathoracic airway hyperresponsiveness. Dysphonia can occur in CC/PVFM and may improve following behavioural treatment of CC.

A review of voice and upper airway function in chronic cough and paradoxical vocal cord movement

Chronic cough and paradoxical vocal fold movement (PVFM) are perplexing conditions. This paper reviews the recent literature in relation to the nature of PVFM and chronic cough and the management of symptoms associated with these disorders. There are similarities in the voice and upper airway symptoms in chronic cough and PVFM. Clinically significant voice symptoms are present in approximately 40% of individuals with chronic cough and PVFM and are similar to those occurring in voice disorders such as muscle tension dysphonia. Chronic cough can be associated with PVFM in a large proportion of cases. Extrathoracic airway hyperresponsiveness is a common underlying mechanism in PVFM and chronic cough. Speech pathology intervention can be effective in controlling symptoms in chronic cough, which suggests that the anatomic diagnostic protocol could be expanded to incorporate this intervention. Chronic cough that fails to respond to medical management should be conceptualized as either due to PVFM or idiopathic. PVFM and chronic cough are not necessarily the result of underlying psychopathology. Chronic cough and PVFM manifest in a range of clinically significant voice and upper airway symptoms. The anatomic diagnostic protocol used in the management of chronic cough could be expanded to include PVFM as a potential cause of cough, and speech pathology intervention as treatment for chronic cough.

Extrathoracic airway responsiveness in children with asthma‐like symptoms, including chronic persistent cough

Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06 +/- 2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF(50)) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF(50) (PD(25)FIF(50)) below the cutoff concentration of < or = 8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32-13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25-1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55-16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94-11.47). In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF(50) and forced expiratory volume in 1 sec (FEV(1)) did not change significantly. The dose of methacholine causing a 20% fall in FEV(1) (PD(20)FEV(1)) and PD(25)FIF(50) values were significantly increased from 2.40 +/- 1.39 to 4.22 +/- 1.13 mg /mL (P < 0.001) and from 1.03 +/- 1.75 to 8.71 +/- 1.21 mg /mL (P < 0.0001), respectively. We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR.

Cough sensitivity and extrathoracic airway responsiveness to inhaled capsaicin in chronic cough patients.

Enhanced cough response has been frequently observed in chronic cough. Recently, extrathoracic airway constriction to inhaled histamine was demonstrated in some chronic cough patients. However, relation between extrathoracic airway hyperresponsiveness (EAHR) and cough sensitivity determined by capsaicin inhalation is unclear in each etiological entity of chronic cough. Seventy-seven patients, with dry cough persisting for 3 or more weeks, normal spirometry and chest radiography, and 15 controls, underwent methacholine bronchial provocation test and capsaicin cough provocation test. Elicited cough number and flow-volume curve was examined after inhalation of capsaicin to evaluate cough sensitivity and EAHR. Thirty-three patients, with postnasal drip, showed normal extrathoracic airway responsiveness, and 27 of them showed normal cough sensitivity to capsaicin. Cough sensitivity was enhanced in 14 patients with cough variant asthma (CVA) who showed bronchial hyperresponsiveness; EAHR to inhaled capsaicin was present in 12 of them. The remaining 30 patients were tentatively diagnosed as idiopathic chronic cough (ICC). Eleven ICC patients showed enhanced cough sensitivity and EAHR to inhaled capsaicin while 19 patients showed normal values. These results indicate that cough sensitivity is closely related with extrathoracic airway responsiveness during capsaicin provocation in some chronic cough patients. EAHR and enhanced cough sensitivity to inhaled capsaicin may be a part of mechanism developing chronic cough.

Damage of the pharyngeal mucosa and hyperresponsiveness of airway in sinusitis

Background: In sinusitis bronchoconstriction is supposed to originate from pharyngobronchial reflexes triggered by seeding of the inflammatory process into the pharynx. Objective: Our aim was to evaluate whether in sinusitis bronchial and extrathoracic airway (EA) dysfunction correlate with morphologic abnormalities of the pharyngeal mucosa. Methods: We performed histamine inhalation challenge, nasal lavage, and nasopharyngeal biopsies in 24 nonasthmatic patients with exacerbation of chronic sinusitis. The histamine PC 20 was the threshold of bronchial responsiveness, and that causing 25% fall in maximal midinspiratory flow was the threshold of EA responsiveness (PC 25MIF 50). Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (BHR) or EA hyperresponsiveness (EAHR). PC 20 and PC 25MIF 50 values were related to clinical data, nasal lavage fluid eosinophils, pharyngeal epithelium and basement membrane thickness, and density of submucosal vessels and nervous fibers. Results: The PC 20 was closely related to PC 25MIF 50 ( p = 0.0004). Ten patients had EAHR, 9 had combined EAHR and BHR, and 5 had neither EAHR nor BHR. EAHR was strongly associated with epithelial thinning, and BHR with long-standing sinusitis, a lower PC 25MIF 50, increased submucosal nerve density and increased nasal lavage fluid eosinophils. Conclusions: Our findings suggest that in nonasthmatic patients with sinusitis, pharyngeal damage may contribute to airway dysfunction by favoring the access of irritants to submucosal nerve endings, with activation of constrictive reflexes to the EA. Proliferation of sensory neurons, consequent to long-lasting pharyngeal inflammation, may cause more severe EA narrowing and activate pharyngobronchial reflexes. (J Allergy Clin Immunol 1997;100:52-7.)

Methacholine Responsiveness of Bronchial and Extrathoracic Airway in Patients with Chronic Cough

BACKGROUND: Chronic cough, defined as a cough persisting for three weeks or longer, Is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, arid gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. METHODS: 111patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patieots with wheeze 22 patients with dyspnea; 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1,) and 25% fall in n axiital midinspiratory flow (PC25MIF50) were used as bronchial and extrathoracic hyperrespornsiveness. RESULTS: There were four response patterns to methacholine challenge study HEIR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in S patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BI-IR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze mad/or dyspnea, BHR was more common than EAHR. CONCLUSION: These results show tint among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

Are asthma-like symptoms due to bronchial or extrathoracic airway dysfunction?

SummaryPatients with asthma-like symptoms may not have asthma but obstruction of the extrathoracic airway (EA). To evaluate if dysfunction of the EA causes asthma-like symptoms, we assessed bronchial and EA responsiveness to inhaled histamine in 441 patients who presented with at least one of three key symptoms—cough, wheeze, dyspnoea—but had neither documented asthma nor bronchial obstruction.The histamine concentrations causing a 20% fall in forced expiratory volume in 1 s (PC20FEV1) and a 25% fall in maximal mid-inspiratory flow (PC25MIF50) were used as respective thresholds of bronchial and EA responsiveness. Values 8 mg/mL or less indicated bronchial (B-HR) or EA hyper-responsiveness (EA-HR). The influence of concurrent upper respiratory tract diseases, such as post-nasal drip (PND), pharnygitis, laryngitis and sinusitis, was also assessed. We found four response patterns to the histamine challenge: EA-HR in 26·5% of the patients, B-HR in 11·1%, combined EA-HR and B-HR in 40·6%, and no-HR in 21·8%. Cough was reported by 79% of the patients, wheeze by 53%, and dyspnoea by 40%. Patients with cough as the sole presenting symptom (34·2%), as compared with those with wheeze and/or dyspnoea (20%), had significantly greater probability of having EA-HR (OR 5·35, 95% Cl 3·25-8·82) and lower probability of having B-HR (OR 0·45, Cl 0·28-0·70); patients with cough plus wheeze and/or dyspnoea (45·8%) had significantly greater probability of having both EA-HR and B-HR than either those with cough alone (OR 2·48, Cl 1·49-4·13), or those with wheeze and/or dyspnoea but not cough (OR 1·74, Cl 1·36-2·22). EA-HR alone or combined with B-HR was strongly associated with EA diseases, particularly pharyngitis and PND. Cough was significantly associated with PND, either when it was the sole symptom (OR 2·16, Cl 1·14-4·09) or when it was combined with wheeze and/or dyspnoea (OR 3·53, Cl 1·97-6·33).Our results suggest that extrathoracic airway dysfunction may account for asthma-like symptoms, particularly chronic cough. This abnormality seems to be sustained by chronic diseases of the upper respiratory tract.

Extrathoracic and intrathoracic airway responsiveness in sinusitis

Background: Asthma associated with sinusitis is supposed to be sustained by bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors. Objective: The study was designed to evaluate the relationship between EA responsiveness and bronchial responsiveness in sinusitis. Methods: We performed histamine inhalation challenge in 106 patients with chronic sinusitis, during disease exacerbation and after treatment with antimicrobials and nasal flunisolide (100 μg daily) for 2 weeks. Forced expiratory volume in 1 second (FEV 1) and maximal mid-inspiratory flow (MIF 50) were the respective indexes of bronchial and EA narrowing; the histamine concentrations causing a 20% fall in FEV 1 (PC 20) and 25% drop in MIF 50 (PC 25MIF 50) were used as thresholds of bronchial and EA responsiveness. Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR). Results: During sinusitis exacerbation 76 patients had EA-HR, which in 46 was associated with B-HR. The values of PC 20 were closely related with those of PC 25MIF 50 ( p < 0.001). EA-HR and B-HR were strongly associated with pharyngitis. After treatment, mean PC 25MIF 50 and PC 20 were significantly increased ( p < 0.001). The improvement of PC 25MIF 50 was closely related to that of PC 20 ( p < 0.001) and to the decrease in neutrophils in nasal lavage ( p < 0.05). EA-HR reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in 12. Conclusions: Our findings suggest that in sinusitis, B-HR may be sustained by constrictive reflexes originating in pharyngeal receptors, made hypersensitive by seeding of the inflammatory process. (J A LLERGY C LIN I MMUNOL 1995;95:52-9.)