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[Clinical study on cough variant asthma].

Chronic cough may be the sole presenting manifestation of bronchial asthma (reference 3; Corrao et al, 1979), and "cough variant asthma (CVA)" has been used to categorize such patients. In order to clarify the clinical picture of CVA, we evaluated the clinical history, laboratory data, sputum cytology and pulmonary function in 14 subjects (5 males and 9 females, aged 14 to 65 years) compatible with the following diagnostic criteria: (1) chronic cough persistent for more than 8 weeks, (2) no wheeze nor dyspnea, (3) no rales, (4) no past history of asthma, (5) bronchial hyperreactivity to methacholine proven by Takishima's method (reference 13), (6) effectiveness of bronchodilators against cough, (7) normal chest X-ray film, (8) afebrile and negative CRP, (9) absence of sinusitis and postnasal drip, or if present, they are proved not to be responsible for the cough, and (10) no other causes of cough such as heart disease, prescription of ACE inhibitors, current smoking. The results were as follows. 1) Many of the subjects were atopic, with positive skin tests to one or more common allergens in 10 subjects, elevated serum IgE in 4 subjects, and past history and family history of atopy in 4 and 7 subjects, respectively. 2) Respiratory infection preceded the onset of CVA in 3 subjects. 3) Cough was generally nocturnal, but 2 subjects coughed only in the daytime. 4) FEV1.0% was decreased (less than 70%) in only 2 subjects, whereas V25 was decreased (less than 80% of predicted value) in 11 out of 12 evaluable subjects, which suggested peripheral airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[The practice guideline 'Acute cough' from the Dutch College of General Practitioners; a response from the perspective of pulmonology].

Coughing is one of the most prevalent symptoms for which patients seek medical attention. Acute cough is defined as a symptom that lasts less than 3 weeks, is mostly transient and with minor consequences. Upper airway infections, and especially the common cold, are the main cause of acute cough. Acute cough is only occasionally due to life-threatening causes like severe pneumonia or pulmonary embolism. The Dutch College of General Practitioners has issued a comprehensive, practical guideline for diagnosis and treatment of acute cough. As viral infections are the most prevalent cause of acute cough, the guideline emphasises the need to be as cautious as possible with the prescription of antibiotics. Unfortunately, a paragraph on the causes of reduced cough effectiveness, which may lead to a more complicated course of illness, is missing from this guideline. Hopefully, this guideline will lead to a more standardized approach to patients presenting with acute cough.

Acute Disease↗

The influence of hyperoxia on cough reflex intensity in guinea pigs treated with bleomycin.

Inhalation of high concentration of oxygen produces a lung injury in men and experimental animals. In our previous experiment we have found suppression of cough reflex in healthy guinea pigs after an exposure to 100% O2 for 60 hours. This study was designed to find the effect of hyperoxia on cough reflex in guinea pigs with lungs damaged by bleomycin. We used 48 animals (300-400 g) in two separated experiments. 32 of them were intratracheally injected with 1.5 mg bleomycin (Bleocin, Nippon Kayaku Co., Ltd., Tokyo, Japan) for induction of lung damage according to the method described by Parizada et al (20). 16 animals were given saline, only (control). Animals of experimental group were divided into two subgroups according to the lapse of time from bleomycin application. 13 days after bleomycin application animals of the 1st subgroup (16) were exposed to 100% O2 (8) or to room air (8) for 48 h. Similarly, 20 days after bleomycin application guinea pigs of the 2nd subgroup (16) were exposed to 100% O2 (8) or air (8), respectively. Cough was provoked in conscious animals placed in bodyplethysmograph box by inhalation of citric acid aerosol (0.3 mol/L) before, then 13 or 20 days after bleomycin application, and finally at the end of 48-h exposition to 100% O2 (air). The number of coughs was counted from airflow trace recorded by pneumotachograph. Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals (Urethane, 1.1 g/kg, i.p.) just after the end of oxygen exposition and was evaluated from the interpleural pressure record. The results have shown a tendency to inhibition of citric acid cough reflex in animals 13 days treated with bleomycin and exposed to 100% O2, and significant decrease in citric acid induced cough in animals 20 days treated with bleomycin and exposed to 100% O2. Significant changes were present in cough intensity induced by mechanical stimulation of TBr region of the guinea pigs airway treated with bleomycin and exposed to oxygen, too. (Tab. 1, Fig. 3, Ref: 29.)

Animals↗

Effects of phosphodiesterase 4 inhibitor on cough response in guinea pigs sensitized and challenged with ovalbumin.

BACKGROUND: There is currently considerable interest in the potential value of selective inhibitors of cyclic nucleotide phosphodiesterase 4 in the treatment of asthma. However, whether they influence eosinophilic airway inflammation-associated cough remains unclear. The objective of this study was to investigate the effects of selective phosphodiesterase 4 inhibitor SB207499 on cough response and airway inflammation in guinea pigs sensitized and challenged with ovalbumin. METHODS: Forty sensitized guinea pigs were randomly divided into four groups: control (n = 10), challenge (n = 10), SB207499 (n = 10) and aminophylline (n = 10), then challenged with aerosol of 1% ovalbumin or saline. Two hours later, animals were intraperitoneally injected with either saline, 25 mg/kg of SB207499 or aminophylline. At the 24th hour, the injection was repeated with 2.5 mg/kg and 25 mg/kg SB207499 or aminophylline, then cough response to inhaled capsaicin and airway responsiveness to methacholine inducing a 150% of the peak airway pressure to the baseline (PC150) was measured. Finally, total cell number and differentials in bronchoalveolar lavage fluid were analysed. RESULTS: The cough frequency per 3 minutes and PC150 in the challenge group were (22 +/- 4) times/3 minutes and (198 +/- 54) microg/ml, which were significantly different from (6 +/- 2) times/3 minutes and (691 +/- 81) microg/ml in the control group (P < 0.05, respectively). The injection of 25 mg/kg SB207499 significantly inhibited the increased cough response and airway hyperresponsiveness, the cough frequency and PC150 in guinea pigs were (13 +/- 2) times/3 minutes and (680 +/- 81) microg/ml (P < 0.05), which differed significantly from (18 +/- 2) times/3 minutes and (400 +/- 86) microg/ml after the administration of the same dose of aminophylline (P < 0.05). The inhibition of SB207499 on cough response was dose-dependent. Similarly, SB207499 decreased the total cell number and percentage of eosinophils in bronchoalveolar lavage fluid to (2.1 +/- 0.5) x 10(6)/ml and (20 +/- 5)% respectively, which were significantly different from (3.2 +/- 0.5) x 10(6)/ml and (29 +/- 5)% in the aminophylline group (P < 0.05, respectively) or (4.2 +/- 0.7) x 10(6)/ml and (35 +/- 4)% in the challenge group (P < 0.05, respectively). CONCLUSION: Phosphodiesterase 4 inhibitor may be more useful than aminophylline for cough associated with eosinophilic airway inflammation via inhibiting airway inflammation and airway hyperresponsiveness.

3',5'-Cyclic-AMP Phosphodiesterases↗

Cough reflex changes in local tracheitis.

The authors describe changes in the cough reflex in unanaesthetized cats with experimental local tracheitis. Inflammation was produced by a silk suture fixed in the trachea and cough was elicited by mechanical stimulation of different parts of the respiratory tract mucosa. The resultant cough values (the number of efforts, the intensity of the maximum effort and the intensity of the attack) were compared with the corresponding values in healthy cats. In animals with a tracheal suture, inflammation was confined to the trachea. The intensity of cough elicited by stimulation of this region increased significantly compared with normal (on the 15th to 17th day of inflammation), whereas cough elicited from the laryngopharyngeal and tracheobronchial region did not. On about the 20th day of inflammation the authors found a decrease in the intensity of the maximum effort of cough elicited from the inflamed part of the trachea and a decrease in the intensity of the maximum effort and the intensity of the coughing attack elicited from the laryngopharyngeal and tracheobronchial region. They assume that the decrease could have been due to the development of protective inhibition in central structures participating in integration of the cough reflex.

Animals↗

[The development and safety of cough provocation test by capsaicin inhalation].

OBJECTIVE: To assess the application and the safety of capsaicin cough provocation test by dosimeter method. METHODS: Capsaicin inhalation cough challenge test by dosimeter method was performed on 60 healthy volunteers (group A), 11 subjects with upper respiratory infection (group B), 10 patients with gastroesophageal reflux cough (group C) and 10 patients with asthma (group D). Each subject inhaled doubling concentrations of capsaicin (1.95, 3.90, 7.80, 15.6, 31.2, 62.5, 125, 250, 500, 1,000 micromol/L) by a breath-activated dosimeter until the concentration inducing five or more coughs (C(5)) was reached. The lg C(5) was calculated as the cough reflex sensitivity. General lung ventilation and impedance with impulse oscillometry were measured before and after the cough provocation test. RESULTS: There was no serious side effect of the test in all subjects; two subjects complained of slight nausea; one of heartburn, and three of hoarseness. Before the provocation the values of FEV(1) in group A, B, C and D were (3.6 +/- 0.5) L, (3.7 +/- 0.7) L, (2.7 +/- 0.8) L and (2.1 +/- 0.8) L, compared with (3.6 +/- 0.5) L, (3.7 +/- 0.8) L, (2.6 +/- 0.7) L and (2.1 +/- 0.8) L after the test, the differences being not significant (all P > 0.05). Compared with the measurements after provocation, Zrs was (2.6 +/- 0.8) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.8) mm Hg.L(-1).s(-1) in group A, (2.5 +/- 0.5) mm Hg.L(-1).s(-1) vs (2.6 +/- 0.3) mm Hg.L(-1).s(-1) in group B, (2.7 +/- 0.7) mm Hg.L(-1).s(-1) vs (2.7 +/- 0.7) mm Hg.L(-1).s(-1) in group C, (3.3 +/- 1.5) mm Hg.L(-1).s(-1) vs (3.7 +/- 2.0) mm Hg.L(-1).s(-1) in group D, the differences showed no significance (all P > 0.05 respectively). The lg C(5) value was 2.45 +/- 0.46 in group A, 2.51 +/- 0.20 in group B, 1.52 +/- 0.70 in group C, 2.34 +/- 0.56 in group D. Compared with group A, B and D, the lg C(5) value in group C was significantly different (all P < 0.01 respectively). The lg C(5) value showed no significant difference among group A, group B and group D (all P > 0.05). CONCLUSION: Capsaicin inhalation cough provocation test by dosimeter method is a safe and specific tool for measuring cough reflex sensitivity.

Administration, Intranasal↗

The interaction of dietary antioxidant vitamins and oxidative stress on cough reflex in guinea-pigs after long term oxygen therapy.

Inhalation of high concentration of oxygen produces oxidative stress in men and experimental animals. Our previous experiments showed that the cough reflex is suppressed in guinea pigs after exposure to 100% O(2) for 60 hours. The aim of this study was to determine the effects of dietary antioxidant supplementation with vitamins C and E on hyperoxia-induced oxidative stress in airway and lung tissues directed on cough reflex. The experimental group (T-H, n=8) was pretreated with vitamins C (500 mg/kg) and E (300 mg/kg) for 4 weeks and subsequently exposed to 100% O(2) for 60 hours. Hyperoxic group (H, n=8) received saline instead of antioxidants and then inhaled 100% O(2) for 60 hours. Cough was induced by inhalation of citric acid aerosol in gradually increased concentration (0.05-1.6 M) at the end of antioxidant therapy and then at the end of exposure to 100% O(2). Cough was also induced by mechanical stimulation of laryngopharyngeal (LPh) and tracheobronchial (TBr) region in anaesthetized animals just 1 hour after the end of oxygen exposure. Our results showed a tendency to a decrease in citric acid-induced cough in hyperoxic animals and an increase in animals with antioxidant therapy after hyperoxia. Antioxidant therapy significantly unblocked hyperoxia-induced down-regulation of cough (P=0.004). Significant changes also were obtained from mechanically-induced TBr cough [2.5(1-4) vs. 1.0(1-2); P<0.01] between the experimental and hyperoxic (control) animals. In conclusion, our results indicate a protective effect of antioxidant supplementation on oxidant-mediated cough depression.

Animals↗

Testing of cough reflex sensitivity in children suffering from allergic rhinitis and common cold.

Cough associated with upper respiratory tract disorders is a common and troublesome problem in children and little is known about the etiology of this type of cough. This study examined the capsaicin cough sensitivity (CS) in children suffering from allergic rhinitis (AR) and upper respiratory tract infection (URI), comparing it with that in healthy children taken as controls (C). CS to capsaicin, spirometry, skin prick tests, and nose-throat examination were performed in 61 children grouped by the diagnosis of AR, URI, and C. The results, in order of C vs. AR vs. URI, expressed as a geometric mean (+/-95% CI) log(10) muM of capsaicin for C2 (the lowest concentration of capsaicin in mumol/l required to induce >or=2 coughs) were: 1.8 (1.6-1.9) vs. 1.0 (0.8-1.2) vs. 0.48 (0.2-0.8), P<0.001 and for C5 (the lowest concentration of capsaicin in mumol/l required to induce >or=5 coughs) 2.9 (2.8-2.9) vs. 2.6 (2.5-2.6) vs. 2.1 (2.0-2.3), P<0.05. We found that CS in children with AR, even when tested out of pollen season, was significantly heightened compared with controls. CS in children with URI was extremely high compared with both C and AR groups. We conclude that pathological processes in the nose of any etiology could cause a sensitization of the cough reflex with decreased cough threshold during asymptomatic period of AR. Cough also is enhanced by acute inflammation in the upper airways in nonatopic children.

Adolescent↗

Patient education about cough: effect on the consulting behaviour of general practice patients.

The aim of this general practice study was to examine how the consulting behaviour of patients with a cough was affected when the tasks and responsibilities of patients, practice nurses and general practitioners were reorganized. In four 'average' single-handed general practices the effects on the consulting behaviour of patients of a rational practice policy on cough and the provision of systematic patient education on cough were compared with patient behaviour in four matched control practices. Changes of behaviour were measured in 548 patients who consulted for cough at least twice, in two successive autumn-winter periods. Significantly more patients in the experimental practice changed their behaviour to follow the practice guidelines than did patients in the control practices (56% versus 30%, P less than 0.001). The proportion of patients who continued to consult in the approved manner was greater among patients receiving intervention (66% versus 29%, P less than 0.001). This was equally true for patients who had suffered less than four episodes of cough or more than four episodes. The more often the patients received the education, the more effective it was. All patients who consulted the general practitioner for cough during the first autumn-winter period filled in a cough diary during the second period. From this it appeared that the intervention did not result in patients delaying consultation when they had a cough lasting longer than three weeks or one with 'serious' symptoms. It would appear that a rational practice policy and the provision of patient education can stimulate patients to modify their consulting behaviour. This could result in a reduction in the costs of health care.

Adolescent↗

Two-year follow up of the management of chronic or recurrent cough in children according to an asthma protocol.

To test the hypothesis that many children with a chronic or recurring cough have asthma, 106 children with cough were treated according to an asthma protocol. At the end of 16 weeks, all but two of the children who completed this phase of the trial were free of cough. At a two-year follow up 97 children were reviewed: 71 were now diagnosed as having an asthmatic condition, 34 of whom required regular medication. The original histories of those who developed asthma were compared with those who had no further respiratory symptoms. The results suggest that many children with a chronic or recurring cough have a mild form of asthma, known as cough variant asthma, which is responsive to asthma therapy. Many will subsequently develop mild to moderately severe asthma. Those who subsequently develop an asthmatic condition are statistically more likely to have a family history of asthma or a personal history of atopy. The children are also more likely to have exercise-induced cough or nocturnal exacerbation of their cough. Managing a persistent or recurring cough according to an asthma protocol could mean that many asthmatic children will be diagnosed and treated earlier in the natural history of their illness.

Asthma↗

Computer-assisted evaluation of some respiratory parameters during voluntary cough.

Three different microcomputers proved to be useful in processing of pressure, flow and volume signals during cough and other respiratory manoeuvres. In young healthy volunteers, values of forced vital capacity, peak expiratory flow and flow at 0.1 s measured during cough were smaller in women than in men due to their smaller body surface and FVC. Compared to forced expiration a sudden and vigorous cough effort, in spite of its shorter duration, resulted in an increased mean flow rate and in similar peak flow reached by expulsion of a smaller volume. Analysis of flow-volume curves indicated higher flow-rates at the beginning (5-10% FEV) and to the end of cough expulsion (65-95% FEV) than in forced expiration. The volume, peak flow and flow 0.1 s from the beginning of inspiration and expiration were practically the same in 5 successive cycles of voluntary cough performed by maximum effort. The mechanisms involved in cough expiration are more automatic than the mechanisms of cough inspiration. A personal computer can be useful for monitoring the increase in PEP, PIP, PEF, PIF, FEV, FIV and in maximum resistance as well as the decrease in compliance observed during cough compared to quiet breathing.

Adult↗

[Effects of respiratory drugs on the cough reflex].

In order to understand the relationship between the cough and respiratory centers in the brain stem, we investigated the effects of respiratory stimulants, pentylenetetrazol (PTZ) and nikethamide (NK), and a respiratory depressant, pentobarbital (PB)on the cough reflex. Coughs were induced in lightly anesthetized dogs by intraarterially into the vertebral artery. The rate (RR), amplitude (RA), and volume (RV) of the respiration and the number (NC) and amplitude (AC) of the cough reflex induced were used as indices. PTZ and NK, even at subthreshold doses for respiratory stimulation, enhanced the cough reflex (NC; not AC). On the other hand, PB at subthreshold doses for a respiratory depression decreased both NC and AC. The above findings suggest that respiratory stimulants generally enhance the cough reflex, and respiratory depressants reduce the cough reflex. Additionally, the thresholds for the cough responses to respiratory drugs are lower than those for the respiratory responses.

Animals↗

Loratadine in the treatment of cough associated with allergic rhinoconjunctivitis.

BACKGROUND: Antihistaminic treatment of allergic asthma or cough-type asthma, including cough associated with allergic rhinocojunctivitis, has been recently reconsidered prospectively since new very potent compounds, nonsedating with anti-allergic properties, are available. OBJECTIVE: The possible effectiveness of loratadine in the treatment of allergic cough was assessed in 20 patients with allergic rhinoconjunctivitis and cough due to Parietaria judaica during the pollen season (April to July 1993). METHODS: Allergic patients were enrolled in a double-blind, placebo-controlled, parallel-group, randomized study, and received loratadine 10 mg/d or placebo in oral tablets for 4 weeks. Occurrence and severity of conjunctival and nasal symptoms, severity and frequency of cough attacks were assessed daily by the patients together with peak expiratory flow evaluation performed twice a day, ie, in the morning and in the evening. Physicians evaluated conjunctival and nasal signs, and spirometry on admission (before treatment), 2 and 4 weeks after treatment. On admission methacholine challenge was also performed to assess PD20. Pollen counts were assessed during the study. RESULTS: According to patients' diary cards, ocular and nasal symptoms were progressively reduced by loratadine treatment (respectively P < .05 and P < .01), as well as cough frequency (P < .05) and cough intensity (P < .01). Peak expiratory flow rate, forced vital capacity, and forced expiratory volume in one second significantly decreased in the placebo-treated group (P < .01), while they were not modified in loratadine-treated patients, who remained normal. CONCLUSIONS: The study suggests that loratadine may be beneficial in the treatment of allergic cough, as well as in rhinoconjunctivitis. Further studies of this may be warranted.

Adult↗

[A case of chronic persistent cough caused by gastro-esophageal reflux].

Although gastro-esophageal reflux (GER) is one of the major causes of chronic persistent cough (CPC) in the USA and in Europe, it is a rare cause of CPC in Japan. We report a rare case of CPC caused by GER, in which treatment with an H2-blocker or with a proton pump inhibitor was successful. A 65-year-old woman had complained of coughing for over 25 years. Her coughing was not alleviated by treatment with a bronchodilator (beta 2-adrenoceptor agonist), an anti-allergic agent, a corticosteroid, or a sedative. GER was considered as a possible cause of her coughing because exacerbation of the coughing was associated with the development of gastrointestinal symptoms (heartburn). Fiberoptic esophagoscopy showed esophagitis and esophageal herniation of the sliding type. Twenty four-hour monitoring of distal esophageal pH showed that the coughing occurred when the pH dropped below 4, and that the pH was less than 4 for about 7% of the whole monitoring time. An H2-blocker or a proton pump inhibitor completely eliminated the symptoms. Therefore, CPC caused by GER was diagnosed. We found that coughing could be induced by instillation of 0.1 N hydrochloric acid at the distal esophagus, and that the coughing was partially inhibited by inhalation of an anti-muscarinic agent (ipratropium bromide) and by esophageal instillation of 4% xylocaine. These data support the "reflex theory". Although CPC caused by GER is rare in Japan, we should remember that GER can be a cause of CPC even in Japanese patients.

Aged↗

Frequency of cough during therapy with ACE inhibitors in Greek hypertensives.

Persistent dry cough is one of the most common side-effects during therapy with ACE inhibitors. The frequency of cough ranges widely (from 0.2% to 15%) in different series, being higher in small studies and smaller in retrospective studies with large number of patients. The aim of the present study was to evaluate the true frequency of cough induced by treatment with ACE inhibitors in Greek hypertensives and to determine various possibly correlated parameters, including sex, duration of therapy and kind and dose of ACE inhibitors. All hypertensive patients followed in our Hypertension Clinic and treated with ACE inhibitors participated in the study. A total of 228 patients, 103 males and 125 females, 24-80 years of age, were treated with ACE inhibitors for a period of 1-41 months: 121 with enalapril, 40 with captopril, 39 with lisinopril, 25 with perindopril and 3 with ramipril. During treatment with ACE inhibitors persistent dry cough occurred in 15 patients, 12 women and 3 men, giving a frequency of 6.58%. Eleven patients (4.82%) volunteered the information and three after questioning. The mean age of these 15 patients with cough was significantly higher from that of the group (n = 213) without cough (64.27 +/- 2.5 vs. 57.9 +/- 0.74 years, mean +/- SEM, P = 0.024). The 12 women with cough were significantly older than the 113 without cough (67.77 +/- 2.8 vs. 57.8 +/- 1.04 years, P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Cough: an otorhinolaryngologist's view].

Persistent cough leads individuals to seek for medical assistance. Clinical investigation, however, may not reveal any alteration within the clinic's sphere of action. Often enough, some professionals treat the symptom as a disease, introducing several medicines, unsuccessfully. The author's experience, as an otolaryngologist, allows to state that many of these professionals ignore the upper aerodigestive tract as a cough-generator site. The present work discusses the alterations on the mentioned tract, which may provoke the cough reflex, reviewing, initially, the cough mechanism and the localization of the specific receptors. Cough is produce by stimulus at the receptor level or far from it. In upper and lower parts of the aerodigestive tract secretions may run to several directions. Secretion from the paranasal sinus is a frequent cause of cough. Acute sinusitis may occur insidiously bringing about the chronification of the inflammation with cough being the only great apparent symptom. Nasal and dental alterations favor sinusal infection. Signs and symptoms, even if minimum, may be detected through an accurate anamnesis. Nasal allergy, laryngitis, post nasal dripping and septal deviation may also produce cough. The ORL examination is, therefore, imperative, and no radiologic examination can substitute for it. An inadequate treatment, particularly of the sinusitis, may bring about a worsening and extension of the initial condition.

Cough↗

Cough and inhibition of the renin-angiotensin system.

PURPOSE: To review clinical and experimental data and epidemiological observations on the incidence and mechanism of dry cough that has been seen with the use of angiotensin converting enzyme (ACE) inhibitors in patients with hypertension. BACKGROUND: With the increasing clinical use of ACE inhibitors in the treatment of both hypertension and heart failure, an annoying dry cough has been observed. Cough has been reported in postmarketing surveillance studies with an incidence of 1-4%, but clinical reports have shown even higher figures, ranging from 1 to 33%. The mean incidence seems to vary between 6 and 14%, depending on the reporting technique used. MECHANISMS: The specific mechanism of this adverse effect is not fully understood. It may be related to effects on the kininogen-kinin (bradykinin) system since the breakdown of bradykinin is prevented by ACE inhibitors. A local accumulation of bradykinin may lead to activation of pro-inflammatory peptides (e.g. substance P, neuropeptide Y) and a local release of histamine. This may also cause cough reflex hypersensitivity. Another more serious adverse effect that has been associated with the use of ACE inhibitors, angioneurotic oedema, may be related to the same mechanisms. MANAGEMENT: The dry cough almost always disappears upon withdrawal of the specific drug. In some instances a dose reduction may lead to improvement. Recent reports have suggested that treatment with calcium antagonists (nifedipine) or non-steroidal anti-inflammatory drugs (indomethacin and sulindac) may eliminate the cough. Antitussive drugs are usually ineffective, as are antihistamines. In some cases the dry cough may disappear spontaneously. The use of provocative tests has not been clinically satisfactory in exploring possible mechanisms or clinical severity. CONCLUSIONS: Dry cough is the most common and annoying, although harmless, side effect associated with the use of ACE inhibitors. Its incidence has probably been underestimated in earlier studies, but it usually disappears on withdrawal of the specific ACE inhibitor.

Angiotensin Receptor Antagonists↗

Effect of frusemide on cough responses to chloride-deficient solution in normal and mild asthmatic subjects.

We studied the tussive effects of a chloride-deficient solution (1.26% sodium bicarbonate). Nine normal volunteers and 10 mild asthmatic subjects were studied. In two double-blind, placebo-controlled, cross-over studies, we assessed the profile of any inhibitory effects that inhaled frusemide had over these responses. Baseline cough challenge was followed by inhalation of either frusemide (40 mg), or 0.15 M NaCl control. Cough was then induced at 0.5, 2, 4 and 6 h after treatment. Forced expiratory volume in one second (FEV1) was measured before and after each challenge. Changes from the baseline cough response due to drug or control were compared nonparametrically at each time point. There was no difference in the sensitivity of normal and asthmatic subjects to the cough challenge (median cough response 15 and 14.5 on control day, 12 and 15 on frusemide day). Frusemide caused sustained inhibition of the cough response in normal subjects (p < 0.05 at 2 h, p < 0.01 at 4 h), but had only a small, nonsignificant effect in asthmatic subjects at 30 min. Falls in FEV1 of asthmatic subjects due to the chloride-deficient solution were not significant, and did not correlate with number of coughs. We conclude that mild asthmatic subjects are less sensitive than normal subjects to the influence of frusemide against low chloride challenge. This observation is not explained by bronchoconstrictor effects of the cough challenge in asthmatic subjects.

Adult↗