Evaluation of ultrasonically nebulised solutions for provocation testing in patients with asthma.

Abstract

The airway response to the inhalation of ultrasonically nebulised distilled water was determined in 55 asthmatic patients and 16 normal subjects. We calculated the dose of water required to induce a 20% reduction (PD20) in forced expiratory volume in one second (FEVy) by measuring the output of the nebuliser and the volume ventilated by each subject. Forty-eight of the asthmatic patients had a PD20 of 9 ml or less but three patients required as much as 24 ml. A PD20 was not recorded in the normal subjects and the challenge was stopped after 33 ml. In 12 patients the challenge was repeated within six months and the airway response was shown to be reproducible at equivalent doses of water. In a separate group of 11 patients there was, however, a highly significant reduction in the percentage fall in FEV, when equivalent doses of water were given on two occasions 40 minutes apart. When the temperature of the inhaled water was increased from 22°C to 36°C eight of 10 patients had a similar change in FEV, with equivalent doses of water. The airways obstruction induced by the inhalation of water was readily reversed with salbutamol administered by aerosol. In some patients a challenge with water or 3.6% saline was repeated after pretreatment with sodium cromoglycate, atropine methonitrate, and verapamil hydrochloride, all given as aerosols. The airway response to the equivalent dose of water or saline was significantly reduced after treatment with sodium cromoglycate but not atropine or verapamil.The measurement of the airway response to the inhalation of ultrasonically nebulised solutions of hypotonic and hypertonic solutions provides a new approach for the investigation of nonimmunologically mediated bronchial reactivity.We have previously measured airway reactivity to these solutions by determining the total volume of inhaled aerosol (that is, ventilation) required to reduce the forced expiratory volume in one second (FEVy) For this reason we have determined the delivered dose required to induce a 20% reduction in FEV1 and compared the responses in FEV, to equivalent doses of water under different conditions. Furthermore, we have measured the proportion of a delivered dose which is retained by the patient. We have also studied the effects of sodium cromoglycate, atropine methonitrate, and verapamil hydrochloride on the airway response to the same dose of inhaled solution. MethodsWe studied 55 patients aged 11-56 years (mean ± SD 28-5 + 10-8 years) with clinically recognised asthma who were taking beta-sympathomimetic aerosols regularly for control of their symptoms. All medications were withheld for at least four hours before any test. The protocol was approved by the ethics review committee and informed consent obtained. Sixteen non-asthmatic subjects volunteered as controls. The FEVI was measured

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

“…It has been shown that a local increase in the osmolarity of the airway surface liquid as a result of respiratory water loss or inhalation of hypertonic saline induces bronchoconstriction in asthmatic patients (30,31). Because bronchial epithelium has both metabolic and secretory functions that mediate both the release of bronchodilators and removal of bronchoconstricting agents (32)(33)(34), it is possible that the absence of AQP5 at the luminal surface of tracheal and bronchial epithelial cells leads to altered extracellular ionic composition that could affect the release and͞or clearance of broncho-reactive substances, resulting in rapid airway responses.…”

Dry air- and hypertonic aerosol-induced bronchoconstriction and cellular responses in the canine lung periphery

“…The release of mediators from inflammatory cells sensitive to transient changes in airway fluid osmolality is believed to initiate AIB and HIB [25,26,41]. Mediator release in vitro [4], and in vivo [5,42] was demonstrated in response to osmotic stress.…”

TRP channels in airway smooth muscle as therapeutic targets

“…For many years it has been known that decreasing the osmolarity of the airway surface liquid by inhalation of hypotonic aerosols is a potent stimulus for airway narrowing in asthmatics (Allegra and Bianco 1980;Anderson et al 1983), aggravating the bronchial hyper-responsiveness that is a characteristic hallmark of the disease. The mechanism by which hypotonicity elicits this response is not clear, however, the effect does persist when airways are isolated (Finney et al 1987).…”