Excessive Bronchial Secretions Research Articles

Swallowing Difficulties with Tracheostomy: A Neuro-Rehabilitation Perspective

Swallowing and breathing are complex and highly coordinated functions. These functions depend on well-coordinated work of many organs with larynx and nervous system playing a critical role. Disturbance in one of these functions negatively affects the other. Surgical airways like tracheostomies are required in a number of situations, including but not limited to major head and neck procedures, cases with decreased lung function, excessive bronchial secretions and cases requiring neuro-rehabilitation when prolonged airway is required for mechanical ventilation. Extensive neuro-rehabilitation is required since patients with surgical airway may develop swallowing difficulties including dysphagia and/or aspiration with a very high prevalence, which can pose a threat to life. This article reviews the current status of the diagnostic and therapeutic modalities for swallowing difficulties with special emphasis on current neuro-rehabilitative strategies. Electronic databases including Medline, Web-of-science, Cochrane Library, and Google scholar were used for literature search. Downloaded articles were subsequently assessed independently by two researchers to determine suitability for inclusion in the study.Key words: Neurorehabilitation, Tracheostomy, Transcranial direct current stimulation, Transcranial magnetic stimulation, swallowing difficulty

Wheezing phenotypes and risk factors in early life: The ELFE cohort.

ObjectiveDifferent phenotypes of wheezing have been described to date but not in early life. We aim to describe wheezing phenotypes between the ages of two months and one year, and assess risk factors associated with these wheezing phenotypes in a large birth cohort.MethodsWe studied 18,041 infants from the ELFE (French Longitudinal Study of Children) birth cohort. Parents reported wheezing and respiratory symptoms at two and 12 months, and answered a complete questionnaire (exposure during pregnancy, parental allergy).ResultsChildren with no symptoms (controls) accounted for 77.2%, 2.1% had had wheezing at two months but no wheezing at one year (intermittent), 2.4% had persistent wheezing, while 18.3% had incident wheezing at one year. Comparing persistent wheezing to controls showed that having one sibling (ORa = 2.19) or 2 siblings (ORa = 2.23) compared to none, nocturnal cough (OR = 5.2), respiratory distress (OR = 4.1) and excess bronchial secretions (OR = 3.47) at two months, reflux in the child at 2 months (OR = 1.55), maternal history of asthma (OR = 1.46) and maternal smoking during pregnancy (OR = 1.57) were significantly associated with persistent wheezing. These same factors, along with cutaneous rash in the child at 2 months (OR = 1.13) and paternal history of asthma (OR = 1.32) were significantly associated with increased odds of incident wheezing. Having one sibling (ORa = 1.9) compared to none, nocturnal cough at 2 months (OR = 1.76) and excess bronchial secretions at 2 months (OR = 1.65) were significantly associated with persistent compared to intermittent wheezing.ConclusionRespiratory symptoms (cough, respiratory distress, and excessive bronchial secretion) were significantly associated with a high risk of persistent wheezing at one year. Smoking exposure during pregnancy was also a risk factor for persistent and incident wheezing.

Cough, a vital reflex. mechanisms, determinants and measurements.

Cough is a natural defense mechanism that protects the respiratory tract from inhaling foreign bodies and by clearing excessive bronchial secretions. As a spontaneous reflex arc, it involves receptors, an afferent pathway, a center processing information, an efferent pathway and effectors. The determinant factor of cough efficacy is the operational volume of the lung, which in turn relies on the strength and coordination of respiratory and laryngeal muscles as well as on lung mechanics. Respiratory muscle weakness and dysfunction as well as expiratory flow limitation and lung hyperinflation may occur in some neuromuscular disorders and in obstructive airway diseases, respectively. Accordingly, all these diseases may show an ineffective cough. In this brief overview, we deal with the determinants of the cough efficacy and the clinical conditions affecting cough efficacy as well as the cough’s efficacy measurements in clinical setting. (www.actabiomedica.it)

Effect of Cornet Device to Clear the Excess Trachea Bronchial Secretions in a 45 Year Old Right Middle and Lower Lobe Pneumonia Patient- A Case Report

A 45- year old woman diagnosed as right middle and lower lobe pneumonia had been referred for chest physiotherapy to evacuate secretions and to improve oxygenation. The X-ray and Computed tomography findings revealed patchy areas of collapse, consolidation and fibrotic strands in right middle and lower lobes. The physical examination findings also confirmed the signs of consolidation and collapse i.e decreased air entry on right side and presence of crepitations. Chest physiotherapy mainly aimed to clear the excess trachea bronchial secretions in pneumonia. Chest physiotherapy with the help of positive expiratory device –Cornet was given twice daily for ten days. Cornet device uses the principle of positive expiratory pressure which creates an airway oscillation inside the airways. This causes thinning down of mucus and the patient can expectorate the secretions with the help of cough or huff. The X-ray findings showed improvement in right lower lobe and there was no radiological evidence of consolidation and collapse post chest physiotherapy. The patient responded to treatment well and she was discharged successfully. It is concluded that the present case study advocates the use of Cornet device to clear the excess tracheobronchial secretions. Cornet device is easy to use without any supervision and the patient may use at home also.

Effect of Manual Hyperinflation on Arterial Oxygenation in Paediatric Patients with Upper Lobe Collapse after Cardiac Surgery

Lung hyperinflation is a technique used by physiotherapists to mobilize and remove excess bronchial secretions, reinflate areas of pulmonary collapse and improve oxygenation. To assess the efficacy of manual hyperinflation in improving arterial oxygenation (PaO2) of paediatric patients with upper lobe lung collapse after cardiac surgery. 18 paediatric patients who had undergone heart surgery and having upper lobe collapse in the post-op ventilation period underwent Manual Hyperinflation (MH). Parameters in cluded arterial oxygen tension (PaO2) value in ABG analysis, clinical findings such as collapsed upper lung lobe in chest radiograph and air entry in auscultation were collected before and 30 min post MH session and documented. The patients were treated with manual hyperinflation delivered using a pediatric AMBU bag with pressure of about 40 cm H 2O. Four sets of eight bag compressions with inflation rate of 10 breaths per minute were delivered during each manual hyperinflation. The result showed that there was a significant improvement in arterial oxygenation (PaO 2) by administering manual hyperinflation therapy for the upper lobe col lapse in post-op ventilated paediatric patients. In this study, it is evident that manual hyperinflation is an effective technique in management of Lung collapse (upper lobe) in post-op pediatric patients. This clearly demonstrates that further research in this area is warranted.

Thoracic sympathectomy for peripheral vascular disease can lead to severe bronchospasm and excessive bronchial secretions.

A 57-year-old male patient suffering from Buerger's disease presented with pre-gangrenous changes in right foot and ischemic symptoms in right hand. Computed tomographic angiography revealed diffuse distal disease not suitable for vascular bypass and angioplasty. Right lumbar sympathectomy was done using a retroperitoneal approach followed 1 year later by right thoracic sympathectomy using a transaxillary approach. Postoperatively, the patient had severe bronchospasm and excessive secretions in the respiratory tract resistant to theophylline and sympathomimetic group of drugs and without any clinical, laboratory and radiological evidence of infection. The patient was started on anticholinergics in anticipation that sympathectomy might have lead to unopposed cholinergic activity and the symptoms improved rapidly. The patient recovered well and was discharged on 10th post-operative day.

Structure-Activity Relationship and Efficacy of Pyridinium Oximes in the Treatment of Poisoning with Organophosphorus Compounds: A Review of Recent Data

During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with organophosphorus compounds. Their mechanism of action is reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus agents. Organophosphorus compounds (OPC) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OPC can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OPC poisoning involves phosphorylation of the serine hydroxyl group at the active site of AChE leading to the inactivation of this essential enzyme, which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the standard pyridinium oximes (pralidoxime, trimedoxime, obidoxime, HI-6) and diazepam are used for the treatment of organophosphate poisoning in humans. Despite of enormous efforts devoted to synthesis and development of new pyridinium oximes as potential antidotes against poisoning with OPC, only four compounds have found their application in human medicine so far. However, they differ in their activity in poisoning with warfare nerve agents and pesticides and there is still no universal broad-spectrum oxime capable of protecting against all known OPC. In this article the latest data on structure-activity relationship of pyridinium oximes including their efficacy in treatment of poisoning with organophosphorus compounds are reviewed.

Atropine Eyedrops for Death Rattle in a Terminal Cancer Patient

"Death rattle" is a term used to describe the noisy sound produced by dying patients caused by the oscillatory movements of secretions in the upper airways. Antimuscarinic drugs, including atropine, scopolamine (hyoscine hydrobromide), hyoscine butylbromide, and glycopyrronium, have been used to diminish the noisy sound by reducing airway secretions. We report on the effectiveness of sublingual atropine eyedrops in alleviating death rattle in a terminal cancer patient. We present a 58-year-old man with pancreatic cancer who was admitted to our hospital because of severe dyspnea, cough, and death rattle with excessive bronchial secretion as a result of multiple lung metastases. We administered 1% atropine eyedrops sublingually to obviate the need for subcutaneous infusions and to prevent somnolence. On the basis of our experience, we conclude that atropine eyedrops, administered sublingually for distressing upper respiratory secretions, may be an effective alternative to the injection of antimuscarinic drugs, or as an option when other antimuscarinic formulations are not available.

Bronchorrhea following Stroke

Background: Stroke-induced excessive bronchial secretion is not rare, but seldom discussed. This study emphasizes its recognition, pathophysiology and treatment. Methods: We prospectively collected data from 19 consecutive stroke patients with bronchorrhea who were admitted within 2 days of stroke onset. Results: Sixteen of them (84%) suffered from ischemic stroke, and 3 patients (16%) had hemorrhage. All of them had brainstem involvement, and 11 of them (58%) had localized lesions in the dorsal lateral medulla. In 15 patients (79%), copious secretion developed within 3 days after stroke onset. The frequency of expectoration was variable with fluctuation, and half of the patients (47%) had to spit every 2–5 min during its climax. The duration of increased secretion ranged from 4 days to over 2 months. Half of the patients (53%) received anticholinergic treatment, and the response was fair to good. Conclusions: Our data provide clinical evidence that stroke patients with dorsal medulla involvement might present with bronchorrhea which seemed to be mediated via a parasympathetic mechanism. This is a treatable disease, and early diagnosis and treatment may greatly reduce patients’ suffering, avoid antibiotics abuse, reduce the incidence of aspiration pneumonia, and shorten the length of hospitalization.

In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of acetylcholine and glutamate

Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical countermeasures. To this end, we employed a repeated measure multivariate design with striatal microdialysis collection and high-performance liquid chromatography analysis to measure changes in concentrations of several neurotransmitters (ACh, glutamate, aspartate, GABA) in the same samples during acute exposure to GB or VX in freely moving guinea pigs. Concurrent with microdialysis collection, we used cortical electrodes to monitor brain seizure activity. This robust double multivariate design provides greater fidelity when comparing data while also reducing the required number of subjects. No correlation between nerve agents' propensity for causing seizure and seizure-related lethality was observed. The GB seizure group experienced more rapid and severe cholinergic toxicity and lethality than that of the VX seizure group. Seizures generated from GB and VX exposure resulted in further elevation of ACh level and then a gradual return to baseline. Glutamate levels increased in the GB, but not in the VX, seizure group. There were no consistent changes in either aspartate or GABA as a result of either nerve agent. These observations reinforce findings with other nerve agents that seizure activity per se contributes to the elevated levels of brain ACh observed after nerve agent exposure.

Pyridinium Oximes as Cholinesterase Reactivators. Structure-Activity Relationship and Efficacy in the Treatment of Poisoning with Organophosphorus Compounds

During more than five decades, pyridinium oximes have been developed as therapeutic agents used in the medical treatment of poisoning with organophosphorus compounds. Their mechanism of action is reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus agents. Organophosphorus compounds (OPC) are used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX and others. Exposure to even small amounts of an OPC can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OPC poisoning involves phosphorylation of the serine hydroxyl group at the active site of AChE leading to the inactivation of this essential enzyme, which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, e.g. atropine, AChE reactivator such as one of the standard pyridinium oximes (pralidoxime, trimedoxime, obidoxime, HI-6) and diazepam has been used for the treatment of organophosphate poisoning in humans. Despite enormous efforts devoted to synthesis and development of new pyridinium oximes as potential antidotes against poisoning with OPC, only four compounds have found their application in human medicine so far. However, they differ in their activity in poisoning with warfare nerve agents and pesticides and there is still no universal broad-spectrum oxime capable of protecting against all known OPC. In this article, we review data on structure-activity relationship of pyridinium oximes and discuss their pharmacological and toxicological significance.

Hyperventilation-induced ST segment elevation mimicking acute myocardial infarction in a comatose patient with tracheostomy

Controlled hyperventilation leading to respiratory alkalosis may induce coronary artery spasm. This manoeuvre is currently used in the diagnosis of Prinzmetal's angina.We describe the case of a comatose patient with tracheostomy in whom hyperventilation, caused by excessive bronchial secretion resulting in partial obstruction of the tracheal cannula, was followed by ST segment elevation mimicking acute myocardial infarction.

Management of primary ciliary dyskinesia: the lower airways

Primary ciliary dyskinesia (PCD) is a genetic disease associated with defective ciliary structure and function. Chronic oto-sino-pulmonary infection is the most common clinical presentation. Patients should be monitored in centres with expertise in PCD. Regular respiratory monitoring consists of lung function tests, adapted to the patient's age, and cough swab or sputum cultures. Chest X-rays are insensitive but the use of high-resolution computed tomography should be considered carefully to avoid excessive radiation. Treatment of the chronic suppuration of the lower airways relies on antibiotics to which the isolated bacteria are sensitive, together with respiratory physiotherapy and exercise to clear excessive bronchial secretions. Bronchodilators and anti-inflammatory agents have no proven benefit and should be prescribed, if at all, on an individual basis. Treatment of the lower airways should always be in conjunction with that of the upper airways. Importantly in PCD, respiratory disease may be controlled with the use of early, adequate and aggressive management.

A pilot study comparing two physiotherapy techniques in patietnts with cystic fibrosis

The flutter is a simple hand held device designed to facilitate the mobilisation of excess bronchial secretions by means of oscillating positive pressure. Traditionally patients at the Johannesburg Hospital Cystic Fibrosis clinic used the active cycle of breathing technique as a means of facilitating secretion mobilisation and clearance. When the flutter became available in South Africa in 1999 many cystic fibrosis patients wanted to change to this technique. Minimal research has been conducted comparing these two techniques. The aim of this pilot study was therefore to determine which technique is more effective in the mobilisation of secretions in cystic fibrosis patients. The pilot study was conducted on seven cystic fibrosis patients (mean age 28 years, range 16-42 years) admitted to the Johannesburg Hospital for antibiotic therapy. The study lasted four days and consisted of two treatment days separated by a washout day on which no physiotherapy was performed. Patients randomised into Group A performed the flutter technique on day two and the active cycle of breathing technique on day four. Group B performed the active cycle of breathing technique on day two and the flutter on day four. The techniques were performed twice a day for 15 minutes. The measurements taken were daily 24-hour sputum samples and daily lung function tests. A questionnaire to determine patient preference to a technique concluded the study. The results showed no statistical difference between the two techniques with regard to sputum weight or lung function (p<0.05). The questionnaire indicated that on a whole, patients had no preference for a technique.

Intoxications aiguës par neurotoxiques organophosphorés : insecticides et armes chimiques

Objective: To review clinical and therapeutic bases of an organophosphate poisoning, either with insecticide or nerve agent. Data sources: References were obtained from computerized bibliographic research (Medline®), from personal data (academic memoir, documents under approbation of the National Defense Office), from Internet’s data. Data synthesis: Generally, organophosphate poisoning occurs during accidental exposure with agricultural insecticide or suicide. The effects of organophosphate coumpounds are due to the inhibition of the enzyme acetylcholinesterase. The intoxication symptoms can be divided into muscarine-like, nicotine-like effects, effects on the central nervous system and symptoms related to the dysfunction of the neuromuscular junction. The interest of biological acetylcholinesterase’s measuring is minimal because it is weakly specific or sensitive. The immediate severity is due to hypoxia. Respiratory failure results from the lack of central drive inflated with excessive bronchial secretions, bronchospasm and respiratory muscles paralysis. The secondary complications are early myopathies whose gravity is correlated with the decrease of acetylcholinesterases, or later neuropathies induced by a different mechanism. Beside the symptomatic mesures, atropine is the specific anticholinergic treatment. When promptly used, oximes can regenerate cholinesterases. The attempted effects of the treatment are mouth dryness, pupilar dilatation and flushing of the skin. Nerve agents are lethal toxics which have a short onset time and produce severe neurological pathology. In a terrorist incident, it is as important to identify rapidly the toxic agent and provide emergency decontamination as to manage medical care. An effective response must be multidisciplinary, involving clinicians, toxicologists, Emergency Medical Service and public’s health personnel.

Bronchoplasty for malignant and benign conditions: a retrospective study of 44 cases.

To study the different operative techniques employed, the problems encountered and the outcome in bronchoplastic procedures both during and after surgery. Forty-four patients with a mean age of 51.6 years (range 15-80 years) underwent bronchoplastic procedures in the period from 1976 to 1998. There were 27 males and 17 females. Forty-two of these had planned surgery. Two trauma patients had emergency surgery. Out of 42 planned operations, 27 suffered from cancer and 15 had benign lesions. Amongst the non-small cell lung cancer (NSCLC) group, the nodal status was N0 in nine patients, N1 in 12 and N2 in six. Bronchial sleeve resection with lobectomy was performed in 24 patients. Six patients had sleeve pneumonectomies. Fourteen others had bronchial sleeve resections without lobectomies, and bronchoplasties for trauma and stricture. Reconstruction was performed in the earlier years with stainless steel wire of 38/40 SS gauge (n=22), vicryl (n=4) and prolene (n=1). More recently, ethibond (n=18) was routinely used for this purpose. Anaesthesia was maintained via oro-tracheal intubation, interrupted when necessary with a short period of intubation of one or the other bronchus through the thoracotomy incision. The mean operating theatre time, including the anaesthesia, was 207 min (range 120-375 min). The duration of stay in the high dependency unit (HDU) was no longer than 3 days. Post-operative problems included excessive bronchial secretions and partial atelectasis (one patient requiring therapeutic bronchoscopy), prolonged mechanical ventilation (n=1) and prolonged air leak (n=1). There was no per-operative, hospital, or 30 day mortality. Four out of 27 cancer patients lived more than 5 years, 12 died between 2 and 5 years, and 11 lived less than 2 years. Whilst bronchoplasties require special anaesthetic techniques and stringent high dependency post-operative care, there is minimal operative morbidity and mortality. Acceptable duration of survival can be expected even in the cancer patients.

The active cycle of breathing techniques—to tip or not to tip?

The active cycle of breathing techniques (ACBT) in gravity-assisted drainage positions is an effective airway clearance regimen for individuals who produce excess bronchial secretions. This study compared the ACBT in positions with and without a head-down tilt. Nineteen subjects (11 men), mean age 37·1 years (range 18–76 years), with bronchiectasis who produced more than 20g of sputum per day and had a mean forced expiratory volume in 1s (FEV 1) of 56·9% predicted (range 23–90% pred.) were studied. There was no significant difference in the wet weight of sputum expectorated when using the ACBT in gravity-assisted drainage positions with or without a head-down tilt. Mean ( sd) score for perception of breathlessness, measured on a visual analogue scale, increased significantly following treatment with a head-down tilt [2·3 (1·6) to 3·3 (2·0) cm, P = 0·02]. There was no significant difference in oxygenation or lung function (FEV 1). Eighteen subjects preferred the ACBT without a head-down tilt. The ACBT in the horizontal position is a simple airway clearance regimen suitable for individuals who produce greater than 20 g of sputum per day. Subjects were less breathless and preferred the ACBT in the horizontal position, thus providing a treatment alternative that may improve adherence in individuals who are required to carry out daily airway clearance treatments.

Usefulness of Miniature Flexible Fiberoptic Bronchoscopy in Children

A miniature flexible fiberoptic bronchoscope (FFB) (Olympus BF-N20) (2.2 mm diameter) was applied to 53 children (20 female subjects) ranging in age from 3 months to 15 years (mean, 4.19 years). Most common indications for bronchoscopy included stridor or weak cry and persistent wheezing or cough unresponsive to inhaled bronchodilators, chest physiotherapy, steroids, and antimicrobial agents. There were no complications. In 38 children (71.6 percent) it was diagnostically useful, particularly for the investigations of upper airway obstruction (66 percent). In 22 children (41.5 percent) it provided guidance for surgical interventions. The instrument was particularly useful during its application in infants with severe upper airway obstruction who otherwise would require open rigid-tube bronchoscopy in the operating room. It was of limited value when excessive bronchial secretions obstructed the view of the working field for which a bronchoscope with a built-in suction channel was needed. It is concluded that this miniature FFB is a useful diagnostic tool in infants and children particularly for obstructed upper airways but has limited applications in children with peripheral airway disease. The 2.2-mm bronchoscope may have its greatest advantage in preterm neonates and intubated infants, where the small glottic or endotracheal tube size renders the 3.5-mm bronchoscope useless.

The Flutter VRP1 as an adjunct to chest physiotherapy in cystic fibrosis

The Flutter VRP1 (Flutter) is claimed to increase the clearance of excess bronchial secretions and to improve lung function and oxygenation, but these claims were based on computer models, laboratory assisted experiments and uncontrolled clinical trials. A prospective randomized clinical trial was undertaken, in subjects with cystic fibrosis, using the active cycle of breathing techniques as the 'gold standard'. The claims could not be substantiated and the possibility of sputum retention was of concern when the Flutter was used as significantly more sputum (P < 0.001) was cleared with the active cycle of breathing techniques alone. There were no significant changes in lung function or oxygenation.

Sensitivity of the cough reflex in patients with chronic cough

Cough may occur in association with excess bronchial secretions and may, therefore, be productive. However, in a proportion of patients the cough is non-productive and a possible association with an enhanced response of the cough reflex has been postulated. Using the irritant capsaicin, the sensitivity of the cough reflex was measured in 363 individuals. A questionnaire was used to divide subjects into three groups: Group A) non-coughing controls; Group B) subjects with non-productive cough; and Group C) subjects with productive cough. The group means (+/- 99% confidence interval (CI)) of the log capsaicin concentration causing two or more coughs (C2) for groups A, B, C were 0.98 (+/- 0.08), 0.64 (+/- 0.09) and 1.04 (+/- 0.23), respectively. The log capsaicin concentration causing five or more coughs (C5) for groups A, B, C were 1.78 (+/- 0.1), 1.16 (+/- 0.12) and 1.54 (+/- 0.25), respectively. Group B was significantly more sensitive to inhaled capsaicin than the other groups (p less than 0.01). No significant difference was observed between groups A and C. Some differences were found when subgroups were examined within groups B and C. In group B, patients with post-nasal drip were found to have a normal sensitivity of the cough reflex and were, therefore, different from the remainder of patients with non-productive cough. In group C, patients with bronchiectasis and current infection showed an increase in the sensitivity of their cough reflex. It is concluded that cough can occur in association with either excess mucus production leading to productive cough or an increase in the sensitivity of the cough reflex, possibly leading to non-productive cough.