Jack A. Kastelik

Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis

Background: It has been proposed that the pH of airway lining fluid may regulate the fractional exhaled concentration of nitric oxide (FeNO) in respiratory disease. Methods: FeNO, exhaled breath condensate (EBC) pH, and EBC concentrations of nitrite plus nitrate (NO2/NO3) were compared in 12 subjects with stable asthma, 18 with stable cystic fibrosis (CF), and 15 healthy control subjects. Eight of the CF patients were studied on a separate occasion at the start of a pulmonary exacerbation. Results: FeNO was significantly greater in asthmatic subjects than in control subjects (mean 35 v 9 ppb, p<0.001). EBC pH, however, was similar in the asthmatic and control groups (median 5.82 v 6.08, p = 0.23). Levels of NO2/NO3 were on average higher in EBC samples from asthmatic subjects, but the difference was not significant. In patients with stable CF both the FeNO (mean 4 ppb, p<0.001) and EBC pH (median 5.77, p = 0.003) were lower than in the control group. Levels of EBC NO2/NO3 (median 29.9 μM; p = 0.002) in patients with stable CF, in contrast, were significantly higher than in control subjects. During CF exacerbations, EBC pH was further reduced (median 5.30, p = 0.017) but FeNO and NO2/NO3 were unchanged. Conclusions: These findings demonstrate a dissociation between EBC pH and FeNO in inflammatory airways disease.

Evaluation of impulse oscillation system: comparison with forced oscillation technique and body plethysmography

To the Editor: We read with interest the study by Hellinckx et al. 1, comparing the techniques of impulse oscillation, forced oscillation and body plethysmography. The impulse oscillation system (IOS) was recently introduced by Jaeger (IOS Enrich Jaeger, Hoechberg, Germany) and its clinical potential is due to its relatively easy acquisition of data. Subjects perform tidal breathing in the upright position without any forced expiratory manoeuvres. This method could therefore potentially acquire broad usage, especially among patients with poor coordination. However, our limited experience with IOS suggests that its wider utilization will be problematic. Conversely, body-box plethysmography is an established method that …

EXPRESSION AND CHARACTERIZATION OF THE INTRACELLULAR VANILLOID RECEPTOR (TRPV1) IN BRONCHI FROM PATIENTS WITH CHRONIC COUGH

TRPV1 is a modulator of noxious stimuli known to be important in the cough reflex. We have compared the expression of TRPV1 in normal human airways and those from patients with chronic cough and found that there is up regulation in airways smooth muscle in disease. This increased expression appears to be intracellular and we have therefore examined the role of intracellular rat and human TRPV1 activity was found using intracellular calcium signalling with human intracellular TRPV1 being located in a thapsigargin insensitive compartment. Increase in TRPV1 activity may have a role in the airway hypersensitivity seen in chronic cough.

Investigation and management of chronic cough using a probability-based algorithm

Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8 weeks were studied. Their age (median (range)) was 60 (16–88) yrs and cough duration 5.9 (0.2–65) yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.

Chronic persistent cough in the community: a questionnaire survey.

BackgroundChronic cough is a common symptom which causes significant levels of morbidity. It is becoming increasingly well characterised by research taking place in specialist cough clinics, where successful treatment rates are high. However, there is a paucity of data regarding the symptom complex of chronic cough in the community. This report details the results of a postal questionnaire survey sent to individuals requesting further information on chronic cough.Methods856 chronic cough questionnaires were sent out to members of the public who requested an information sheet following a national UK radio broadcast. Information regarding demography, history of cough, previous treatment and physical, psychological and social effects of the cough was elicited.Results373 completed questionnaires were returned. Mean age was 65.3 years (SD 12.0, range 9–88 years). 73% were female and 2% current smokers. Median duration of cough was 6.5 years. 66% had no other coexisting respiratory diagnosis, whilst 24% reported asthma. Of those who responded, 91% had consulted a general practitioner regarding the cough and of them, 85% had been prescribed some sort of treatment. 61% had seen at least one hospital specialist. Commonly reported associated physical symptoms included breathlessness (55%), wheeze (37%), fatigue (72%) and disturbed sleep (70%). Incontinence occurred in 55% of women. Similarly, the majority reported psychological effects such as anger or frustration (83%), anxiety (69%) and depression (55%). 64% felt that the cough interfered with their social life.ConclusionChronic cough causes a high level of morbidity in the community, which results in a correspondingly high rate of healthcare utilisation. Demography and symptomatology seems to be similar to that reported from specialist centres, but successful treatment of the cough was uncommon, despite a high number of medical consultations in both primary and secondary care. If understanding of this debilitating but eminently treatable condition is enhanced, management of chronic cough will improve and many patients will be helped.

Role of long term antibiotics in chronic respiratory diseases.

Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions.

Gender differences in airway behaviour

We were surprised to read in the exhaustive and, some might say, exhausting review of gender differences in airway behaviour by Becklake and Kauffmann1 that the most common respiratory symptom—namely, cough—deserved only a single sentence and was then dismissed. In fact, the most dramatic gender difference in airway sensitivity is seen with the cough reflex. We studied 163 consecutive, healthy, non-smoking volunteers (90 women, mean age 32 years) with an inhalation cough challenge of five one-second inhalations of 10% citric acid delivered from a Mefar dosimeter. Women coughed over 50% more than men …

Inhaled corticosteroids in chronic obstructive pulmonary disease: a pro–con perspective

Current guidelines limit regular use of inhaled corticosteroids (ICS) to a specific subgroup of patients with chronic obstructive pulmonary disease (COPD) in whom the forced expiratory volume in 1 s is <60% of predicted and who have frequent exacerbations. In these patients, there is evidence that ICS reduce the frequency of exacerbations and improve lung function and quality of life. However, a review of the literature suggests that the evidence available may be interpreted to favour or contradict these observations. It becomes apparent that COPD is a heterogeneous condition. Clinicians therefore need to be aware of the heterogeneity as well as having an understanding of how ICS may be used in the context of the specific subgroups of patients with COPD. This review argues for and against the use of ICS in COPD by providing an in‐depth analysis of the currently available evidence.

Spontaneous pneumomediastinum: a rare complication of bronchial asthma.

Pneumomediastinum is a rare complication of an acute exacerbation of asthma. We describe a 28-year-old female who was admitted to hospital with acute severe exacerbation of asthma and developed a spontaneous pneumomediastinum (SPM) with associated subcutaneous emphysema. She was successfully managed conservatively. On follow up there was resolution of the subcutaneous emphysema and the pneumomediastinum, clinically and radiologically. SPM although usually a self-limiting condition, can occasionally be life threatening. Therefore, it is important to raise the awareness of this potential complication of asthma.

Comparison of the effect of high-dose inhaled budesonide and fluticasone on adrenal function in patients with severe chronic obstructive pulmonary disease

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of respiratory-related morbidity and mortality. Inhaled steroids are frequently used in patients with moderate to severe disease and may lead to adrenal suppression. OBJECTIVES: The aim of this study was to compare the effect of inhaled budesonide/formoterol with inhaled fluticasone/salmeterol in severe COPD. METHODS: It was a prospective open-label crossover study of 22 patients. Adrenal suppression was measured by overnight urinary cortisol/creatinine ratio. The measurements were taken while patients were on either combination for at least 4 weeks. RESULTS: A total of 12 patients completed the study. The mean age was 64 years (8 males, 4 females). The mean FEV1 was 1 L (range, 0.5-1.8). There was no significant difference in adrenal suppression measured by overnight urinary cortisol/creatinine ratio (budesonide 5.2 ± 4.3, fluticasone 4.7 ± 3.1; 95% CI -2.2 to 1.2; P = 0.52) and urinary cortisol concentration (budesonide 51 ± 53, fluticasone 43 ± 31 [nmol/l]; 95% CI -35 to 20; P = 0.56). CONCLUSION: Inhaled budesonide and fluticasone have no significantly different effect on adrenal function in moderate to severe COPD. The adverse event profile of high-dose inhaled steroids should not influence the choice of medication.