Cough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least one history of aspiration pneumonia and age-matched healthy elderly people.
Patients were prospectively and consecutively recruited from those referred and admitted to the Geriatric Unit, Tohoku University Hospital for treatment of pneumonia from May 2007 to April 2008. Pneumonia was diagnosed by the presence of pulmonary infiltration on chest radiograph and computed tomography (CT) and according to systemic inflammation as determined according to white blood cell (WBC) count and C-reactive protein (CRP). The criteria for pneumonia were established according to the pneumonia guidelines of the Japan Respiratory Society . In the current study, aspiration was defined according to the Japanese Study Group on Aspiration Pulmonary Disease as pneumonia in a patient with predisposition to aspiration because of dysphagia or swallowing disorders . In our unit, all the elderly patients (> 75 years old) with pneumonia had fasted at the time of admission. When they recovered after treatment such as antibiotics drip infusion, we considered letting them start eating with their alert consciousness. We estimated their swallowing reflex before making the decision to start eating. The swallowing reflex was induced by a bolus injection of 1 ml distilled water into the pharynx through a nasal catheter (8 Fr). The subjects were unaware of the actual injection. Swallowing was identified by submental electromyographic (EMG) activity and visual observation of characteristic laryngeal movement. EMG activity was recorded from surface electrodes on the chin. The swallowing reflex was evaluated by the latency of response, timed from the injection to the onset of swallowing . If the latency of swallowing reflex was > 5 seconds, we regarded the patients as suffering from impaired swallowing function, e.g. aspiration pneumonia.
During the entry period, 41 patients with pneumonia without an apparent past- and present-history of stroke were admitted to our 20 bed geriatric unit, and 34 patients (83%) were diagnosed as aspiration pneumonia. We performed simple chest X-ray in all of them. Among 34 patients, we performed chest CT scan in 30 patients. All 34 patients showed characteristic images of infiltrates compatible with aspiration pneumonia in the posterior segment of any of the lobes and/or lower lobe by simple chest X-ray and/or CT scan. Of 34 patients, 2 patients died and 3 patients eternally tracheostomized. Of 29 recovered patients, due to the difficulty of urge-to-cough estimation, we excluded patients with dementia using the mini-Mental State Examination (MMSE). Of 29 patients who recovered from aspiration pneumonia, 18 subjects with a MMSE score < 24 were excluded. Three patients with apparent paralysis were excluded. Finally, 8 patients (3 men) with aspiration pneumonia (70–88 years old) were enrolled for this study. From 6 patients among 8, we obtained brain images with non-contrast CT scan. The CT scan revealed that 2 patients had infarct in the deep region of middle cerebral artery territory, 2 patients in the superficial region (cortical or adjacent subcortical infarcts) of middle cerebral artery territory, and 1 patient in both the deep and superficial region of middle cerebral artery territory. One patient had infarct in the superficial region of the posterior cerebral artery territory. The diameters of all infarcts were within 1 cm.
Eleven age and sex-matched healthy elderly people (72–84 years old) as control subjects were recruited from the community by advertisement. None of the subjects were demented (MMSE scores > 23). All control subjects were never-smokers, and had no previous history of pneumonia and other respiratory diseases. None of the patients or controls were taking medication which might affect cough sensitivity such as antitussives, narcotics, or ACE inhibitors. A CT scan was obtained from only one control subject.
Cough reflex sensitivity and urge-to-cough
Cough reflex and urge-to-cough was examined more than 3 months after negative conversion of C reactive protein after pneumonia had responded to antibiotics treatment (median 24 days, range 13–30). At the time of evaluation, the subjects were in a stable state until at least 3 months before. Simple standard instructions were given to each subject.
We evaluated the cough reflex sensitivities using citric acid because we had previously used this method to observe depressed cough in the elderly [1, 3]. Cough reflex sensitivity to citric acid was evaluated with a tidal breathing nebulized solution delivered by an ultrasonic nebulizer (MU-32, Sharp Co. Ltd., Osaka, Japan) . The nebulizer generated particles with a mean mass median diameter of 5.4 μm at an output of 2.2 ml/min. Citric acid was dissolved in saline, providing a two-fold incremental concentration from 0.7 to 360 mg/ml. Based on "cough sound", the number of cough was counted both audibly and visually by laboratory technicians who were unaware of the clinical details of the patients and the study purpose. Each subject inhaled a control solution of physiological saline followed by a progressively increasing concentration of citric acid. Increasing concentrations were inhaled until five or more coughs were elicited, and each nebulizer application was separated by a 2-min interval. The cough reflex sensitivities were estimated by both the lowest concentration of citric acid that elicited two or more coughs (C2) and the lowest concentration of citric acid that elicited five or more coughs (C5).
Immediately after the completion of each nebulizer application, the subject made an estimate of the urge-to-cough. The modified Borg scale was used to allow subjects to estimate the urge-to-cough . The scale ranged from "no need to cough" (rated 0) and "maximum urge-to-cough" (rated 10). The urge-to-cough scale was placed in front of the subjects and the subject pointed at the scale number, which was recorded by the experimenter. To assess the intensity of the urge-to-cough, subjects were recommended to ignore other sensations such as dyspnea, burning, irritation, choking and smoke in the throat. Subjects were told that their sensation of an urge-to-cough could increase, decrease, or stay the same during the citric acid challenges, and that their use of the modified Borg scale should reflect this.
The study protocol was approved by the local ethics committee and informed consent was obtained from all subjects. Data are expressed as mean (SD) except where specified otherwise. The Mann-Whitney U test or the chi-square test were used to compare patients with controls. A p value of < 0.05 was considered significant.