Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma which is often associated with airways inflammation. However, some patients with allergic rhinitis and no clinical evidence of asthma also exhibit BHR. This study therefore investigated whether inflammatory cell infiltrate is present in the induced sputum of nonasthmatic subjects with allergic rhinitis during the pollen season and examined its relationship with airway hyperresponsiveness to inhaled methacholine and adenosine 5'-monophosphate (AMP).Twenty subjects (12 allergic rhinitis, eight nonallergic controls) underwent methacholine and AMP challenge and sputum induction with hypertonic saline on separate days. Cell differentials were calculated from whole sputum samples.A significantly greater number of eosinophils was found in the sputum of nonasthmatic subjects with allergic rhinitis compared to that of nonallergic controls, their median (range) percentages being 17.5 (4±47) and 1.5 (0±5) (p<0.001) respectively. Although sputum eosinophilia failed to be significantly associated with methacholine responsiveness (rs= -0.50; p=0.095), the provocative concentration of AMP causing a 20% fall in forced expiratory volume in one second correlated strongly and significantly with the absolute number of eosinophils (rs=-0.73; p=0.007). Eosinophil cationic protein levels in the sputum of rhinitic subjects were significantly elevated compared to controls and correlated with eosinophil number (rs=0.67; p=0.017).These findings support the view that bronchial eosinophilia alone is insufficient to cause asthmatic symptoms. Diverse agonists for assessing bronchial hyperresponsiveness are selectively associated with airway inflammation in allergic rhinitis. Eur Respir J 2000; 15: 30±35.

Assessment of airway responsiveness by bronchoprovocation and bronchodilatation tests is important in the diagnostic work-up protocol of bronchial asthma and it would be convenient to undertake both tests on the same occasion. However, it is not known whether this can be done accurately. Therefore, this study evaluated the effect of a prior bronchial provocation test on the bronchodilator response to salbutamol after spontaneous recovery of the forced expiratory volume in one second (FEV1) in a group of asthmatic subjects. On two separate occasions at the same time of day, concentration-response studies with inhaled histamine or methacholine, or a sham challenge with normal saline were carried out in a blinded, randomized manner. Changes in airway calibre were followed as FEV1 and agonist responsiveness expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). After either spontaneous recovery or a fixed-duration wait of 45 min (when appropriate), the subjects received 2x100 microg of salbutamol from a metered dose inhaler with a spacer. The bronchodilator response to salbutamol was expressed as a percentage of initial FEV1 (deltaFEV1% init). Bronchial challenge with both agonists failed to alter significantly the airway response to salbutamol, with the deltaFEV1% init mean value (range) being 16.9% (9.0-31.9) and 17.5% (11.6-31.2) on the sham and histamine/methacholine challenge day respectively. It was shown that the degree of bronchodilatation achieved after salbutamol 200 microg is not affected by prior bronchoprovocation testing when enough time is allowed for the airways to recover spontaneously to baseline forced expiratory volume in one second. Thus evaluation of airway responsiveness by both bronchial provocation tests and bronchodilator testing can be assessed reliably within a few hours in asthmatic patients.

The small decrease in airway responsiveness to neurokinin A after administration of lysine acetylsalicylate by inhalation suggests that endogenous prostaglandins may play a contributory protective role in the airway response to neurokinin A in human asthma. Eur Respir J., 1996Respir J., , 9, 1139Respir J., -1145 Sensory neuropeptides, such as substance P (SP) and neurokinin A (NKA), exhibit a range of features which may be relevant to the pathophysiology of asthma, including contraction of airway smooth muscle, increased vascular permeability, mucus secretion and activation of cholinergic neurotransmission [1]. Immunocytochemical studies have demonstrated the presence of sensory neuropeptides and their receptors within the upper and lower airways both in man and rodents [2][3][4]. Although compared with rodents the nerve fibres containing sensory neuropeptides are less dense in human airway tissue, recent studies on necroscopic tissue, bronchoalveolar lavage fluid, and induced sputum have shown increased amounts of SP in the airways of asthmatics compared to controls [5][6][7]. Different authors have demonstrated that both SP and NKA produce dose-related bronchoconstriction when administered by inhalation to asthmatic subjects, NKA being more potent than SP and asthmatic subjects being more responsive than normal subjects [8][9][10][11][12].The mode of action by which sensory neuropeptides elicit bronchoconstriction in asthma is not well understood. The bronchoconstrictor effect of nebulized NKA in asthmatic patients is inhibited by prior treatment with nedocromil sodium [10,13], suggesting that this response may be evoked indirectly rather than through direct stimulation of airway smooth muscle. There is some support for an action of sensory neuropeptides in eliciting prostaglandin synthesis. Recent in vitro studies support the view that many of the biological responses of the sensory neuropeptides may result from the local release of bioactive prostanoids [14][15][16].In line with the notion that administration of bronchoactive drugs by inhalation achieves maximum effect with smaller doses, BIANCO and co-workers [17,18] have recently shown that the potent cyclooxygenase inhibitor, aspirin administered as an aerosol of lysine acetylsalicylate (L-ASA) solution elicits better protection against nonspecific stimuli in the airways of asthmatics than when given orally. Using this alternative experimental approach, we intend to expand our previous observations with other nonspecific agonists [19,20], by evaluating the relative contribution of contractile prostaglandins to the airway response provoked by inhaled NKA in asthmatic subjects.

Abstractmetabisulphite, 6 adenosine 5′-monophosphate (AMP), 7 and bradykinin. 8 Although the mechBackground -Inhaled frusemide exerts a protective effect against broncho-anisms underlying the protective effects of this drug against these different forms of proconstriction induced by several indirect stimuli in asthma which could be due to vocation in asthma are not yet clear, an inhibitory effect on airway nerves has been interference of airway nerves. A randomised, double blind, placebo controlled suggested. In support of this, inhaled frusemide has been shown to inhibit the cough response study was performed to investigate the effect of the potent loop diuretic, fru-induced by low chloride aerosols 9 and to produce dose-dependent inhibition of the consemide, administered by inhalation on the bronchoconstrictor response to neuro-tractile response of airways smooth muscle induced by the stimulation of cholinergic and kinin A (NKA) and histamine in 11 asthmatic subjects.non-adrenergic non-cholinergic (NANC) nerves in guinea pigs. 10Methods -Subjects attended the laboratory on four separate occasions to receive The peptide tachykinin, neurokinin A (NKA), exhibits a range of features which may nebulised frusemide (40 mg) or matched placebo 10 minutes prior to bronchial chal-be relevant to the pathophysiology of asthma, including contraction of airway smooth muscle, lenge with NKA and histamine in a randomised, double blind order. Changes in increased vascular permeability, mucus secretion, and activation of cholinergic neuroairway calibre were followed as forced expiratory volume in one second (FEV 1 ) and transmission.11 12 Immunocytochemical studies have demonstrated the presence of NKA and its responsiveness to the agonists was expressed as the provocative concentration related receptors within the human airways. subjects NKA elicits dose-related bronchoconstriction, with the asthmatic subjects being Results -Compared with placebo, inhaled frusemide reduced the airway responsive-more responsive than normal individuals. [15][16][17][18][19] The mode of action by which NKA elicits ness to NKA in all the subjects studied, the geometric mean (range) values for bronchoconstriction in asthma is not well understood. The bronchoconstrictor effect of PC 20 NKA increasing significantly (p<0.001) from 130.3 (35.8-378.8) to 419.9 nebulised NKA in asthmatic patients is inhibited by prior treatment with nedocromil (126.5-1000) g/ml after placebo and frusemide, respectively. Moreover, a small sodium, 17 20 suggesting that this response may be evoked indirectly rather than through direct but significant change in airway responsiveness to histamine was recorded stimulation of airway smooth muscle. In addition, there is recent evidence for an action of after frusemide, their geometric mean (range) PC 20 values being 0.58 (0.12-3.80) NKA in eliciting bronchoconstriction through activation of cholinergic pathways. 21 and 1.04 (0.28-4.33) mg/ml after placebo and frusemide, respectively. We have therefore investigated the effect of ...

Airway responsiveness to histamine and NKA is reduced by BDP to the same extent. As a result of these findings, provocation with NKA is unlikely to provide additional useful information in the assessment of airway inflammation in asthma.