Effectiveness of a heat and moisture exchanger in preventing hyperpnoea induced bronchoconstriction in subjects with asthma.

The effect of a heat and moisture exchanger, a device with hygroscopic material for conditioning inspired air, on hyperpnoea induced bronchoconstriction was studied in nine non-smoking volunteers with asthma, aged 19-32 years. Each had previously shown an increase of at least 100% in specific airways resistance (sRaw) to isocapnic hyperpnoea with dry air. On two separate days the subject performed isocapnic hyperpnoea with dry air at 60-70 l min-1 for five minutes. Before, immediately after, and five minutes after completion of a test sRaw measurements were made. Heat and moisture exchangers were placed in the breathing circuit on one of the two days. All subjects had an increase in sRaw of 100% or more without the heat and moisture exchangers (average increase 300%) but were protected from bronchoconstriction with the devices in place (average increase 7%) (p less than 0.005). The exchanger's resistance to airflow was less than 1 cm H2O for flow rates of 100 l min-1. A heat and moisture exchanger designed as a facemask or mouthpiece may allow a person with asthma to exercise without the need for prophylactic drugs.     

Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma.

Previous work suggests a role for mast cell derived mediators in exercise induced asthma. The contribution of newly generated contractile prostaglandins to exercise induced asthma was assessed by using a potent and orally active thromboxane (TP1) receptor antagonist, GR32191. The effect of 120 mg GR32191 on exercise induced asthma was observed in 12 asthmatic subjects. For the exercise challenge the subjects performed six minutes of treadmill exercise, breathing dry air at a work load that had previously been shown to induce a fall in FEV1 of 25% or more from the pre-exercise baseline. No effect of GR32191 on pre-exercise baseline airway calibre was evident. There was no significant difference in the mean maximum percentage fall in FEV1 from baseline after exercise between drug and placebo (placebo 30.2%, GR32191 day 31.6%). It is concluded that the thromboxane antagonist GR32191 has no effect on exercise induced asthma. This suggests that prostaglandins, including PGD2, that act via the thromboxane receptor do not have an important role in exercise induced asthma.     

The effect of prompt local cooling on oedema formation in scalded rat paws

A standardized, reproducible burn model on rat paw was used and the effect of prompt local cooling on the oedema formation was measured using a newly developed non-invasive method. A transient reduction in oedema formation was observed lasting for a longer period of time with decreasing temperature down to 0 degrees C and increasing cooling time up to 120 min. The decrease in oedema formation was followed by an increase towards or above the amount of oedema in untreated scald injury. This post-cooling increase in oedema formation was related to the temperature and the exposure time of the cooling fluid. The immediate effects of cooling are most likely due to local restriction of the blood flow as a result of cold-induced vasoconstriction. The increase of the oedema formation after the cooling period may be due to reactive hyperaemia.     

Effect of hypothermia on blood-flow responses in pedicled groin flaps in rats.

Cooling is widely used for preserving tissues such as kidneys before transplantation and for preserving extremities before replantation. Hypothermia has also been shown to be effective in the temporary storage of free flaps. However, in the intact living body, cooling can be damaging to tissue and the body system. We used a custom-designed clamping method (after flap elevation, occlusion and release of the flap-feeding artery) and continuous laser Doppler flowmetry to investigate the effects of hypothermia on blood flow and postocclusive reactive hyperaemia in the flaps. The animal model used was the partially elevated epigastric flap of adult Sprague-Dawley rats. In the hypothermia group (n=12), the core temperature and the flap temperature were allowed to fall during anaesthesia. At core temperatures of 34.58 degrees C and 338 degrees C and after rewarming of the rat, the feeding artery was occluded for 30 s and 120 s to observe the changes in blood flow and postocclusive reactive hyperaemia in the flap. In the control group (n=12), the core temperature was maintained at more than 378 degrees C throughout the experiment. To compare the flap blood-flow responses to occlusion of the femoral artery in the hypothermia group and the control group, the postocclusive reactive hyperaemia periods (i.e. blood flow above baseline after clamp release) were analysed. Statistical analysis of the responses showed that the magnitude (P=0.024), duration (P<0.001) and amplitude (i.e. peak flow) (P=0.037) of postocclusive reactive hyperaemia were significantly decreased in the hypothermia group. Our results suggest that hypothermia significantly decreases blood flow and postocclusive reactive hyperaemia in the rat epigastric flap. This may increase the risk of ischaemic flap complications unless rewarming is performed.     

Pattern of carbon dioxide stimulated breathing in patients with chronic airway obstruction

The pattern of stimulated breathing during carbon dioxide inhalation was studied in a group of 21 patients with severe irreversible airways obstruction (mean FEV1 = 0.9 litre, mean FEV1/FVC% = 50%). Carbon dioxide rebreathing experiments were performed, the ventilatory response being defined in terms of total ventilation (V) and CO2 sensitivity (S). Breathing pattern was defined by the changes in tidal volume (delta VT) and respiratory frequency (delta f) and the maximum VT achieved (VTmax). Contrary to some previous studied no significant relationship could be demonstrated between the severity of airway obstruction (FEV1/FVC%, Raw) and the ventilatory response to rebreathing (V, S, delta VT, delta f, VTmax). However, measurements of dynamic lung volume (FEV1, FVC, IC) were found to be significantly correlated with the breathing pattern variables (delta VT, delta f, VTmax). Resting PaO2 and PaCO2 were significantly correlated with delta VT but not delta f. Results indicate that the degree of airway obstruction does not dictate the ventilatory or breathing pattern response to carbon dioxide induced hyperpnoea. In contrast it is the restriction of dynamic lung volume, by limiting the VT response, that appears to determine the ventilatory and breathing pattern response in patients with severe airway obstruction.     

Reactive hyperaemia in the hind limbs of rabbits. II. The effect of changes in oxygen tension and temperature.

The effect on reactive hyperaemia of variations in oxygen content of the inspired air and in tissue temperature, was studied by electromagnetic flowmetry in the hind limbs of rabbits. Flowmetry was used together with oxygen polarography to compare recovery time of blood flow and recovery time of oxygen tension in muscle tissue during reactive hyperaemia. After occlusions lasting more than 10 seconds; recovery time of oxygen tension was much shorter than recovery time of blood flow. Breathing of different oxygen concentrations induced relatively small changes of reactive hyperaemia. After increasing tissue temperature all variables of reactive hyperaemia were reduced following 10-60 seconds' occlusion. On the other hand, after 5 minutes' occlusion percentual repayment and recovery time increased significantly. During hypothermia, percentual repayment and recovery time were reduced significantly after 5 minutes' occlusion. Thus, the time-response curves for percentual repayment and recovery time during hyper-and hypothermia crossed each other when occlusion time was extended beyond 60 seconds. Normalization of oxygen tension when blood flow was still increased seems to exclude that oxygen deficiency per se is the only cause of reactive hyperaemia. Oxygen deficiency may be a contributory factor in the initiation of vasodilation during circulatory arrest and may possibly be of importance in the first part of reactive hyperaemia. The results of changing the tissue temperature suggested that metabolites which are accumulated during circulatory arrest, maintain the increased blood flow, at least after release of longer occlusions.     

Airway response to methacholine during exercise induced refractoriness in asthma.

To investigate the mechanisms contributing to refractoriness in exercise induced asthma a methacholine challenge test was performed 30 minutes before and 30 minutes after two exercise tests 45 minutes apart. Exercise was performed by 12 asthmatic patients while they were breathing cold air. There was a smaller airway response to the second exercise test than to the first, though there was wide variation between subjects. The response to the second methacholine challenge was reduced in some patients but showed no significant change overall. Refractoriness to exercise induced asthma positively correlated with a reduced response to methacholine. These data suggest that mediator depletion does not fully explain refractoriness.     

Causes of gas exchange impairment during general anaesthesia

This review describes the distribution of ventilation and blood flow in the anaesthetized subject, during spontaneous breathing and after muscle paralysis. Within minutes after induction of anaesthesia, the diaphragm is shifted cranially (supine position), functional residual capacity is reduced and collapse of dependent lung regions can be seen by means of computed tomography. These changes occur whether anaesthesia is intravenous (barbiturate) or inhalational (halothane) and whether ventilation is spontaneous or mechanical. Ventilation is subsequently reduced in dependent lung regions, whereas blood flow is preferentially distributed to the lower lung regions. This causes a ventilation/perfusion mismatch, the hall-mark of which is shunt. Additional factors such as airway closure and release of hypoxic pulmonary vasoconstriction may contribute to the gas exchange disturbance. The major features of the lung function impairment are already present during spontaneous breathing in the anaesthetized subject, and muscle paralysis adds only little to the disturbance.     

Relation of the hypertonic saline responsiveness of the airways to exercise induced asthma symptom severity and to histamine or methacholine reactivity.

BACKGROUND: Conflicting views exist over whether responsiveness of the airways to hypertonic saline relates to non-specific bronchial hyperresponsiveness measured by histamine or methacholine challenge. The bronchoconstrictor responses to exercise and hypertonic saline are reported to be closely related, but the relationship between the symptoms of exercise induced asthma and airway responsiveness to hypertonic saline is not known. METHODS: In 29 asthmatic patients with a history of exercise induced asthma, the response to an ultrasonically nebulised hypertonic saline (3.6% sodium chloride) aerosol, measured as the volume of hypertonic saline laden air required to produce a fall in forced expiratory volume in one second (FEV1) of > or = 20% (PD20), was compared with the concentration of histamine (PC20; group 1) and methacholine (PC20; group 2) producing a 20% fall in baseline FEV1 and exercise induced asthma symptom severity score (groups 1 and 2). The hypertonic responsiveness was determined in a dose-response manner to a maximum dose of 310 1 and the exercise induced asthma symptom severity was scored on a scale of 0-5. RESULTS: Of the 29 patients, 23 (79%) were responsive to the hypertonic saline, with PD20 values ranging from 9 to 310 1. A significant correlation was found between the PD20 hypertonic saline and the exercise induced asthma symptom score. There was no significant correlation between the PD20 response to hypertonic saline and the histamine PC20 or methacholine PC20. The exclusion of those subjects who failed to respond to hypertonic saline improved the relationship between hypertonic saline and methacholine PC20. No significant correlation was found between the exercise induced asthma symptom score and histamine PC20 or methacholine PC20. CONCLUSION: These findings suggest that hypertonic saline responsiveness bears a closer relationship to the severity of exercise induced asthma symptoms than to the non-specific bronchial hyperresponsiveness measured by histamine or methacholine reactivity.     

The Influence of Arm Ischaemia and Arm Hyperaemia on Subclavian and Vertebral Artery Blood Flow in Patients with Occlusive Disease of the Subclavian Artery and the Brachiocephalic Trunk: A Peroperative Study

A peroperative study of blood flow and flow direction was performed in series of patients with occlusive disease of the subclavian artery. Particular attention was focused on the flow variations caused by arm ischaemia and postischaemic hyperaemia and on the effect of injection of a vasodilator into the distal subclavian artery. the effect on blood flow and flow direction was measured with the aid of an electromagnetic flowmeter. During arm ischaemia induced by an inflated cuff on the arm, the subclavian flow diminished, as did the vertebral artery flow when it was retrograde. If the vertebral artery flow was anterograde, it increased during arm ischaemia. the postischaemic hyperaemia caused an increase of the subclavian flow and of reversed vertebral flow. If the vertebral flow was anterograde, it diminished during the postischaemic hyperaemia. Similar findings were obtained with intra-arterial injection of a vasodilator. the large amount of blood flow passing through the vertebral artery, as well as the flow variations caused by reactive arm hyperaemia, emphasize the role of this artery as a collateral vessel to the upper limb in cases of the subclavian steal phenomenon.     

The influence of arm ischaemia and arm hyperaemia on subclavian and vertebral artery blood flow in patients with occlusive disease of the subclavian artery and the brachiocephalic trunk. A peroperative study.

A peroperative study of blood flow and flow direction was performed in series of patients with occlusive disease of the subclavian artery. Particular attention was focused on the flow variations caused by arm ischaemia and postischaemic hyperaemia and on the effect of injection of a vasodilator into the distal subclavian artery. The effect on blood flow and flow direction was measured with the aid of an electromagnetic flowmeter. During arm ischaemia induced by an inflated cuff on the arm, the subclavian flow diminished, as did the vertebral artery flow when it was retrograde. If the vertebral artery flow was anterograde, it increased during arm ischaemia. The postischaemic hyperaemia caused an increase of the subclavian flow and of reversed vertebral flow. If the vertebral flow was anterograde, it diminished during the postischaemic hyperaemia. Similar findings were obtained with intra-arterial injection of a vasodilator. The large amount of blood flow passing through the vertebral artery, as well as the flow variations caused by reactive arm hyperaemia, emphasize the role of this artery as a collateral vessel to the upper limb in cases of the subclavian steal phenomenon.     

Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.     

Influence of circulating alpha adrenoceptor agonists on lung function in patients with exercise induced asthma and healthy subjects.

The influence of circulating noradrenaline (in this context primarily a non-selective alpha agonist) and the alpha 1 selective agonist phenylephrine on bronchial tone, blood pressure, and heart rate was studied in eight patients with exercise induced asthma and eight age and sex matched controls. All subjects refrained from taking treatment for at least one week before the trial. The agonists were infused intravenously in stepwise increasing doses of 0.04, 0.085, 0.17, and 0.34 micrograms/kg a minute for noradrenaline and 0.5, 1.0, 2.0, and 4.0 micrograms/kg a minute for phenylephrine. At the highest dose the plasma concentration of noradrenaline was about 30 nmol/l, resembling the concentrations found during intense exercise, and that of phenylephrine was about 400 nmol/l. Both agonists caused dose dependent and similar increases in blood pressure in the two groups. Despite clearcut cardiovascular effects (systolic and diastolic blood pressure increased by about 40-50/25-30 mm Hg), neither agonist altered lung function, as assessed by measurements of specific airway compliance (sGaw), peak expiratory flow (PEF), or end expiratory flow rate, in either group. It is concluded that circulating alpha agonists, whether alpha 1 selective (phenylephrine) or non-selective (noradrenaline), fail to alter basal bronchial tone in patients with exercise induced asthma or in healthy subjects.     

Exercise-induced airways constriction

Airway conductance was measured in a body plethysmograph at different lung volumes before and after graded exercise. In 14 out of 19 patients, mostly asthmatics, airway conductance fell significantly after exercise. These subjects also showed other signs of an increased bronchial reactivity to different stimuli, including forced breathing, hyperventilation, and cold air, but they had no exogenous allergy. The exercise-induced bronchoconstriction could be blocked by atropine in six of the nine patients tested. Exercise-induced bronchoconstriction in patients with clinical and physiological evidence of increased airway reactivity thus seems to be primarily mediated via a vagal reflex, probably from hyperresponsive airway mechanoreceptors reacting to increased ventilatory flow or lung distension. No relation was found between PaCO₂ or pH and the severity of airways constriction. Cromoglycic acid failed to block the exercise reaction in five of the six hyperreactive patients tested. In addition to or following the vagal reflex a disturbed relation between beta and alpha receptors in bronchial muscles or a release of humoral spasmogens may contribute to the progression of post-exercise airways constriction.     

Acute and chronic airway obstruction in children

Airway obstruction is more common in children than in adults. This is because of subtle anatomical differences in the childhood airway and an increased propensity to infection. Effects of obstruction manifest more quickly in children because of a smaller airway diameter, reduced physiological reserve and easily fatigued respiratory muscles. The signs of airway obstruction differ between upper and lower airway obstruction, and in the spontaneously breathing and ventilated child because of the differences in the mechanics of breathing in each of these situations. The anaesthetist must be able to recognize risk factors for airway obstruction such as a history of respiratory symptoms, including sleep-disordered breathing, and high-risk groups, such as ex-preterm infants. The anaesthetist must also be able to recognize the signs of airway obstruction in the awake, anaesthetized and paralysed child. Upper airway obstruction may be moderate, as in many cases of tonsillar or adenoidal hypertrophy and laryngomalacia, or severe, as in some upper respiratory tract infections such as epiglottitis, croup or bacterial tracheitis. Lower airway obstruction is most commonly seen in children with reactive airways secondary to atopic asthma, viral-associated wheeze or chronic lung disease of prematurity. It can also accompany chronic infection and bronchiectasis, as in cystic fibrosis or primary ciliary dyskinesia. Pulmonary hypertension can develop in any child with chronic airway obstruction and is an additional risk factor for complications including death during anaesthesia. This article outlines some of the issues in acute and chronic airway obstruction in children. Where possible up-to-date anaesthetic management or algorithms will be referenced.     

Exercise induced asthma and endogenous opioids.

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five asthmatic patients and five normal volunteers breathing cold air during exercise. In four of the patients the effect of an infusion of naloxone on FEV1 was also measured during exercise induced asthma. Exercise produced acute bronchoconstriction in all asthmatics, characterised by a fall in FEV1; whereas no change occurred in normal subjects. There was no difference in plasma met-enkephalin, beta endorphin, and ACTH concentration between the two groups. Infusion of naloxone neither prevented nor worsened exercise induced asthma. These data suggest that endogenous opioids probably do not play a part in the development of exercise induced asthma.     

Effect of different bronchodilators on airway smooth muscle responsiveness to contractile agents.

"Functional antagonism" is often used to describe the general relaxant effect of beta 2 agonists and xanthines and their ability to protect the airways against bronchoconstrictor stimuli. This study in guinea pig isolated trachea addresses the question of whether the capacity of these drugs to protect against constrictor stimuli is related to smooth muscle relaxation. Three antimuscarinic drugs were also examined to determine whether antagonism of mediators other than muscarinic agonists might contribute to bronchodilatation by these antimuscarinic drugs. Terbutaline (1.1 x 10(-7), 2.2 x 10(-7) M), theophylline (2.2 x 10(-4), 4.4 x 10(-4) M), and enprofylline (5.2 x 10(-5), 1.0 x 10(-4) M) relaxed the tracheal tension that remained after indomethacin treatment. They did not, however, alter the carbachol concentration-response curve significantly. In addition, neither theophylline (2.2 x 10(-4) M) nor terbutaline (1.1 x 10(-7) M) altered histamine induced contraction. Atropine sulphate, glycopyrrolate, and ipratropium bromide had EC50 values of 10(-9) - 10(-8) M for relaxation of carbachol induced contractions, whereas concentrations of 10(-6) - 10(-3) M or greater were required to relax contractions induced by allergen and nine other non-muscarinic mediators. It is suggested that bronchodilatation by antimuscarinic drugs in vivo is due to inhibition of acetylcholine induced bronchoconstriction alone and that beta 2 agonists and xanthines have poor ability to protect airway smooth muscle against constrictor stimuli. Hence mechanisms other than bronchodilatation and "functional antagonism" should be considered to explain the protection against constrictor stimuli in asthma seen with beta 2 agonists and xanthines.     

Effect of inhaled piriprost (U-60, 257) a novel leukotriene inhibitor, on allergen and exercise induced bronchoconstriction in asthma.

The leukotrienes, a group of oxidative metabolites of arachidonic acid, have potent pharmacological actions on human airways. We have investigated the effects of a leukotriene synthesis inhibitor, piriprost (U-60, 257) administered by inhalation on allergen and exercise induced bronchoconstriction in 12 subjects with allergic asthma. Subjects underwent diagnostic challenges with allergen and treadmill exercise to define the strengths of the stimuli required to reduce the FEV1 to about 25% of baseline (PS25). On separate study days subjects inhaled either piriprost 1 mg or vehicle placebo, followed 15 minutes later by the PS25 allergen or exercise. The FEV1 was measured at regular intervals before and after challenge up to 60 minutes. After allergen challenge in six subjects peak expiratory flow (PEF) was measured for the following 20 hours. When compared with placebo, inhalation of piriprost had no significant protective effect on the fall in FEV1 at any time point within 60 minutes of allergen or exercise challenge. In the four subjects with a documented late asthmatic reaction 2-12 hours after allergen challenge piriprost had no protective effect when compared with placebo. In the subjects who recorded PEF over 20 hours after allergen challenge there was no significant difference between piriprost and placebo. Piriprost was appreciably more irritant to the respiratory tract than was placebo. On the assumption that inhaled piriprost was bioavailable in the airways, this study casts doubt on any theory of a pivotal role for leukotrienes in the pathogenesis of acute exercise and allergen induced airway bronchoconstriction in asthma.     

Calf blood flow and oxygen carriage after reversal of polycythaemia secondary to hypoxic lung disease.

Reduction of packed cell volume has been recommended as a therapeutic procedure in patients with polycythaemia secondary to hypoxic lung disease. We have investigated the effects of this policy on blood flow and oxygen carriage to the calf in 12 such patients. Packed cell volume was decreased from 0.61 to 0.51 (mean) by isovolaemic haemodilution on a cell separator, with significant reductions in blood viscosity at high and low shear rates. Resting calf blood flow was unchanged but peak flow during reactive hyperaemia increased by 17% and 21% one and seven days after the procedure. Oxygen carriage to the calf at rest was initially unchanged but had fallen by 20% at seven days. During reactive hyperaemia oxygen carriage was not impaired by the reduction in packed cell volume since the rise in blood flow offset any reduction in arterial oxygen content. This study has shown that when blood flow is stressed during reactive hyperaemia oxygen carriage is not compromised by a therapeutic reduction in packed cell volume.     

Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma

BACKGROUND: The production of peroxynitrite, an extremely potent oxidant, is increased in inflammatory lung disease. It is therefore important to measure antioxidant activity against peroxynitrite in epithelial lining fluid to examine the physiological effects of peroxynitrite in the airways of patients with asthma. This study was designed to determine whether peroxynitrite inhibitory activity in induced sputum is correlated with clinical characteristics and airway inflammatory indices in asthmatic patients. METHODS: Inflammatory indices were measured in induced sputum from 25 patients with asthma and 12 normal control subjects. Peroxynitrite inhibitory activity was also measured by monitoring rhodamine formation in sputum samples. RESULTS: Peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients (52.4 (24.5)%) than in normal control subjects (92.1 (3.9)%, p<0.0001). Its activity was significantly correlated with forced expiratory volume in 1 second (FEV(1)) % predicted (r=0.774, p<0.0001) and bronchial hyperreactivity to methacholine (r=0.464, p=0.023). There was a significant negative correlation between peroxynitrite inhibitory activity and the degree of eosinophilic airway inflammation (% eosinophils, r=-0.758, p<0.0001; eosinophil cationic protein, r=-0.780, p<0.0001). CONCLUSIONS: Decreased peroxynitrite inhibitory activity occurs in induced sputum of asthmatic patients. Since even in patients with stable asthma the airway lining fluid lacks peroxynitrite inhibitory activity, large amounts of peroxynitrite, which are further increased during an acute asthma attack, would not be completely inactivated and asthmatic airways might have markedly increased susceptibility to peroxynitrite induced airway injury.