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M Dahlbäck

Publications and source records attributed to M Dahlbäck.

At least 19 recordsLinked to original sources
PubMed1998

Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue.

A high airway concentration might be required for the antiasthmatic efficacy of inhaled glucocorticosteroids (GCS). The topical uptake and retention of GCS in airway tissue were compared for GCS of the inhaled type [budesonide (BUD), fluticasone propionate (FP), and beclomethasone dipropionate (BDP)] and of the noninhaled type (dexamethasone and hydrocortisone). 3H-labeled GCS solutions were administered into rat airways by either perfusion of trachea in vivo, intratracheal instillation, or inhalation. Radioactivity was determined in the airway tissue, lung parenchyma, and plasma 20 min to 24 hr after exposure. Ethanol extracts of exposed tracheas were analyzed by HPLC. Exposed tracheas were also incubated in vitro in buffer, and the released radioactivity was analyzed by HPLC. BUD, FP, and BDP were equally well taken up into the airway tissue; their uptake was 25-130 times greater than that of dexamethasone and hydrocortisone. BUD was shown to form very lipophilic intracellular fatty acid esters (at carbon 21) in the airway and lung tissue after topical application. In large airways 20 min after administration, approximately 70-80% of retained BUD was conjugated. BUD stored in esterified form in the tissue was retained in large airways for a prolonged time, compared with FP and BDP, which do not form such conjugates. The fatty acid conjugation of BUD is reversible in vivo; BUD conjugates are gradually hydrolyzed and free BUD is regenerated. This reversible conjugation may improve airway selectivity, as well as prolong the local anti-inflammatory action of BUD in the airways and might be one explanation for why BUD is efficacious in the treatment of mild asthma when inhaled once daily.

Administration, Inhalation↗
PubMed1997

The effect of treatment with budesonide or PGE2 in vitro on allergen-induced increases in canine bone marrow progenitors.

Increased bone marrow granulocyte-macrophage colony forming units (GM-CFU) in dogs developing allergen-induced airway hyperresponsiveness can be accounted for by a factor(s) present in serum following the allergen challenge. The present study evaluated whether in vitro treatment of bone marrow with budesonide or prostaglandin (PG)E2, prevents allergen-induced bone marrow stimulation. Eight dogs were studied after allergen and diluent inhalation challenges. Budesonide (10[-7] M) or PGE2 (10[-6] M) was added to bone marrow aspirated 24 h after challenge. Budesonide or PGE2 was also added to bone marrow aspirated before challenge, to which serum taken 24 h after challenge was subsequently added. Non-adherent mononuclear bone marrow cells were incubated in the presence of the serum and granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte stimulating factor (G-CSF), or stem cell factor (SCF), and the number of GM-CFU counted. Allergen-induced increases in the number of GM-CFU in bone marrow aspirated 24 h after allergen (P < 0.001) were not attenuated by budesonide or PGE2 treatment (P > 0.05). However, GM-CFU increases in bone marrow aspirated before challenge and incubated with post-allergen challenge serum (P < 0.001) were blocked by either budesonide or PGE2 (P < 0.001). These findings demonstrate that budesonide and PGE2 can act directly on the bone marrow, preventing allergen-induced increases in inflammatory cell progenitor production. This suggests that the bone marrow must be considered as a possible site of action for drugs which attenuate allergen-induced asthmatic responses.

Allergens↗
PubMed1996

Effects of local and systemic budesonide on allergen-induced airway reactions in the pig.

1. In this study, an attempt was made to distinguish between local and systemic effects of low doses of the topical glucocorticoid, budesonide. The effect of aerosolized budesonide administered to the lower airways versus intravenously administered budesonide on the acute and late response to nebulized Ascaris suum extract in the lung, was evaluated in the minipig after active sensitization with purified A. suum antigen. Budesonide was administered once, 1 h prior to A. suum challenge and airway reactions and mediator release were observed for 8 h after allergen challenge. 2. In the budesonide aerosol group (n = 6), 10.2 +/- 1.2 micrograms kg-1 budesonide was given locally and in the budesonide infusion group (n = 5), 5 micrograms kg-1 was given intravenously. The area under the plasma concentration curve for budesonide during the experiment was 11.4 +/- 1.2 and 10.3 +/- 1.2 nM h in the budesonide aerosol and budesonide infusion group, respectively (no significant difference). The lung tissue content of budesonide in the two groups was 45.2 +/- 4.9 and 18.4 +/- 3.5 nmol kg-1 dry tissue, respectively, 8 h after allergen challenge (P < 0.05). For comparison, 6 pigs were given budesonide vehicle as an infusion prior to A. suum challenge. 3. Total lung resistance (RL) increased acutely (maximal response within 15 min) in the budesonide aerosol, budesonide infusion and budesonide vehicle groups (by 91 +/- 40, 150 +/- 86 and 80 +/- 27%, respectively). The acute reaction partially resolved at about 1 h and was followed by a late increase in RL in the budesonide infusion and budesonide vehicle groups (by 251 +/- 148 and 281 +/- 136% at 8 h, respectively). However, no late change in RL was seen in the budesonide aerosol group (7 +/- 24%). 4. Aerosolized budesonide had a protective effect in that it attenuated the late changes in arterial blood gas and pH as well as the late elevation of plasma catecholamines. Budesonide given as an infusion did not protect against the late changes in these parameters. However, budesonide aerosol or infusion did not inhibit the late vasodilation in the bronchial circulation. 5. Histamine and cysteinyl-leukotrienes were released during the acute reaction as measured by urinary concentration of methylhistamine and leukotriene E4 respectively. There was no release of histamine during the late reaction. A late increase in leukotriene E4 was observed in 2 of the budesonide infusion and 3 of the budesonide vehicle pigs, whereas no such increase was seen in any of the budesonide aerosol pigs. 6. Budesonide concentration in lung tissue, but not in plasma at 8 h correlated negatively with the late increase in RL (P < 0.05, r = -0.53, n = 10), whereas budesonide concentration in plasma but not in lung tissue correlated negatively with the late decrease in dynamic compliance (P < 0.05, r = -0.67, n = 12). 7. This study has shown that a single low dose of locally administered budesonide can inhibit the late allergic reaction in the pig lower airways. If budesonide was given as an intravenous infusion in a dose yielding a plasma concentration similar to that seen after the aerosol treatment, the protective effect of budesonide was poor. It may be suggested that the tissue-bound portion of budesonide affects local mechanisms involved in the development of late changes in the airways (RL), although it does not affect the late increase in bronchial blood flow. We conclude that the inhibitory effect of budesonide on the allergen-induced late reaction in the pig airways relates to tissue-bound steroid, and that the systemic component is of less importance.

Administration, Inhalation↗
PubMed1996

Granulocyte function in the airways of allergen-challenged pigs: effects of inhaled and systemic budesonide.

BACKGROUND: Late airways obstruction and eosinophil infiltration after allergen challenge are often seen in human asthma and animal models of allergy. This inflammatory reaction, which may be a link between acute and chronic asthma, is blocked by glucocorticoid pretreatment. However, the role of eosinophils in late airways obstruction and the primary site of action of glucocorticoids, i.e. locally or systemically, have not been fully determined. OBJECTIVES: This study was initiated to find out the role of eosinophils and neutrophils in allergen-induced late airways obstruction in the pig. The effect of pretreatment with budesonide (BUD) given locally or systemically on cellular responses seen within 8 h after allergen challenge was also studied. METHODS: Twenty-five minipigs were actively sensitized with Ascaris suum antigen and challenged under anaesthesia with antigen in the lower airways. Pigs were given BUD as an aerosol (10 micrograms/kg) or an intravenous infusion (5 micrograms/kg) 1 h before allergen challenge. In one group, high doses of BUD (50 micrograms/kg) were infused twice with a 3-h interval before allergen challenge. As a positive control, one group was given the BUD vehicle as an infusion and as a negative control, one group not treated with BUD was given the irrelevant antigen ovalbumin. Eosinophils and neutrophils in lung tissue specimens were detected and levels of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) fluid were measured using specific antibodies against porcine EPO and MPO. RESULTS: The number of eosinophils in lung tissue and BAL fluid and the level of EPO in BAL fluid were significantly increased 8 h after A. suum challenge in pigs not treated with BUD. With regard to possible recruitment and activation of neutrophils the only significant finding was an increase in the number of cells in BAL fluid. The eosinophil numbers and the level of EPO in BAL fluid were shown to be decreased by all BUD treatments in all the compartments studied compared to the positive control. However, the number of eosinophils in lung tissue and EPO levels in BAL fluid did not correlate with the magnitude of the late airways obstruction. CONCLUSION: Although eosinophils are present in the bronchial wall and lumen and are apparently activated, a causative relationship between this granulocyte and the late bronchial obstruction could not be established in this model.

Administration, Inhalation↗
PubMed1995

The effects of an inhaled corticosteroid on oxygen radical production by bronchoalveolar cells after allergen or ozone in dogs.

Both ozone and allergen inhalation increase the capacity to produce oxygen radicals by bronchoalveolar lavage cells in dogs. The purpose of these studies was to determine whether inhaled corticosteroids inhibits these increases in oxygen radical production from bronchoalveolar lavage cells. Six random source dogs were studied after dry air or ozone inhalation (3 ppm, 30 min). Seven random source dogs were studied after diluent or allergen inhalation. The dogs inhaled budesonide (2.74 mg/day) or lactose powder, twice daily for 7 days before ozone and allergen. 90 min after ozone or dry air, and 24 h after Ascaris suum or diluent a bronchoalveolar lavage was carried out. Spontaneous luminol-enhanced chemiluminescence was measured from bronchoalveolar lavage cells (4 x 10(6) cells) for 10 min, followed by a measurement of phorbol myristate acetate (PMA 2.4 micromol/l) stimulated chemiluminescence for 10 min. Both ozone and allergen inhalation caused an increase in PMA stimulated chemiluminescence (P<0.05). Budesonide pretreatment inhibited ozone-induced (P<0.008), but not allergen-induced PMA stimulated chemiluminescence (P>0.90). Both ozone and allergen inhalation caused an increase in the bronchoalveolar lavage neutrophils. Budesonide pretreatment significantly inhibited the ozone-induced (P=0.007), but not the ascaris-induced neutrophil influx (P=0.93). These results demonstrate that ozone, but not allergen, stimulated oxygen radical release and neutrophil influx are attenuated by inhaled corticosteroids. This suggests that luminol-enhanced chemiluminescence from bronchoalveolar lavage cells measures oxygen radicals derived from neutrophils, and that ozone-and allergen-induced bronchoalveolar lavage neutrophilia are caused by different mechanisms.

Administration, Inhalation↗
PubMed1995

Regulatory effects of aerosolized budesonide and adrenalectomy on the lung content of endothelin-1 in the rat.

This study was designed to investigate the effect of inflammation and glucocorticosteroids (GCS) on the content of endothelin-1-like immunoreactivity (ET-LI) in the rat lung. Following intratracheal instillation of Sephadex beads, which induces a long-lasting inflammation in the lung, there was an increase in the lung content of ET-LI measured by RIA. This increase was abolished by locally administered aerosolized budesonide at doses that had only minor systemic effects (measured as a reduction in body weight). In a second series of experiments, rats were subjected to surgical adrenalectomy in order to reduce the levels of endogenous GCS. This procedure elevated the ET-LI levels in the lungs. In contrast, neither adrenalectomy nor high doses of budesonide administered systemically affected the concentration of ET-LI in the kidney. It is concluded that the lung ET levels are elevated in inflammatory conditions and that this increase is highly sensitive to locally administered GCS. Endogenous GCS may, directly or indirectly, play a role in the regulation of lung ET content but there seems to be no general GCS effect on basal tissue levels of ET.

Administration, Inhalation↗
PubMed1994

Why do medical nebulizers differ in their output and particle size characteristics?

Previous work done on the characterisation of nebulizers has focused on gravimetrical output and particle/droplet size distribution at various air flow rates. This paper investigates six different nebulizers, with regard to droplet generation and separation properties, at a single air flow rate. Droplet generation and separation properties were measured with laser diffraction and impactor techniques. For each of the nebulizers the air velocity was calculated and both liquid and air volumetric flow rate was measured. The primary generated droplets (nebulizer without impaction baffle) had a mean size of between 15 microns and > 500 microns. The secondary generated droplets (nebulizer with baffle) were in the size range of 1 to 10 microns. It was found that the baffle system of the investigated nebulizers could be described according to ordinary impaction theory. The mass median diameters (MMD) of these nebulizers were found to be dependent on air velocity (vg), and ratio of liquid to air volumetric flow rate (Ql/Qa). In all of the nebulizers, between 93% and 99% of the generated primary droplets were caught by the baffle system which resulted in a very low output. Thus, the nebulizers examined do not appear to be optimised, with regard to observed droplet generation and baffle arrangements, if secondary droplets with a size approximately 1 micron are desired. By changing the design at the primary generation point, air velocity (vg) and liquid to air flow rate (Ql/Qa), the primary generated droplet size could be decreased. This would result in an increase in the number concentration of smaller droplets that pass the baffle system.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1994

Selective deposition of inhaled aerosols to mechanically ventilated rabbits.

We have studied selective deposition of tracer aerosols to specific sites in airways and peripheral regions of the rabbit lung by varying droplet size and breathing pattern. The different breathing patterns were controlled by a Servo Ventilator 900C and different droplet sizes (polydisperse) were generated by an air jet nebulizer (MA2) using two types of impactor vessels (MMD 2.3 and 4.1 microns). Three tracer aerosols were evaluated; Evans blue dye, 99mTc-DTPA and monodisperse fluorescent polylatex spheres (PLS). When we combined large droplets with "rapid-shallow" breathing (central deposition mode, CDM), 30% of the aerosol was deposited in the central airways. When small droplets were combined with "deep-slow" breathing (peripheral deposition mode, PDM) 60% was deposited in the peripheral part of the lung. The different detection techniques showed similar results but gave complementary information. Since detection of the radiolabelled aerosol was more sensitive than the other methods, less aerosol could be given allowing a more precise evaluation of the deposition, both from the macro autoradiographic images as well as from the well counter measurements. In order to investigate how far into the lung periphery the aerosol could be detected, we used PSL microspheres. PLS could be detected in the alveolar region by a fluorescent light microscope. However, a complete selectivity can not be obtained by aerosol delivery. The different technique used to reach selective deposition, showed that it is only possible to deposit the aerosol either more to the central or more to the peripheral parts of the respiratory tract in small subjects.

Administration, Inhalation↗
PubMed1994

Behavior of nebulizing solutions and suspensions.

A compressed air source is needed to run a jet nebulizer; its operating pressure affects the aerosol flow through the nebulizer, the quantity of drug and/or solution leaving the nebulizer, and the droplet size. With increasing pressure, the output (gravimetric change during nebulization) will increase and the droplet size decrease. The temperature of the nebulizing solution will decrease by as much as 10 degrees C due to energy loss from evaporation of droplets. Other important considerations in nebulizer therapy are taste, pH and viscosity of the solution. For those drugs which cannot be dissolved, the nebulizing behavior is different. In nebulizing suspensions, the drug particles must be micronized to a mass median diameter of 1-2mum to give optimal output conditions from jet nebulizers with a droplet size of 3mum mass median diameter. The solid drug particles leave the nebulizer through the medium of the droplets, and when a solid drug particle is larger than the droplet it will become trapped in the nebulizer. This has been illustrated in a separate experiment in which 0.5mg/ml budesonide was nebulized from eight different nebulizers. The droplet size as well as the output--calculated from the quantity of drug remaining in the nebulizer after 10 min nebulization--varied with type of nebulizer. A preferable way of determining drug delivery to a patient is to collect the aerosol on a filter during normal breathing and then analyse the drug content on the filter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1994

Basic nebulizer function.

The main function of a jet nebulizer is to aerosolize the contained liquid. The primary generation point is the orifice where the compressed air expands and increases in velocity. At this point the expanding air induces an underpressure and liquid is sucked up to the air orifice where it meets the rapidly expanding air. Droplets from the liquid surface are carried away with the airstream towards the baffle system. After cut-off by impaction on the baffle surface, secondary generation occurs on the baffle as droplets are produced due to high air velocity. Several different designs of nebulizer are available. The differences cause variation in the output characteristics; for example, in the liquid output and droplet size distribution. There is also disparity between individual nebulizers of the same brand. This is due to manufacturing errors. Repeated use of a single nebulizer over time causes ageing. This, in turn, causes the critical points of droplet generation to change. The most significant changes are the small increases in the diameter of the air orifice. This may be due to mechanical wear from the compressed air source or to extensive cleaning procedures. The effect of the increasing diameter, as seen by the user, is decreased driving pressure at a constant rate of air flow. There is also an effect on the output characteristic of the nebulizer. With decreasing driving pressure the air velocity decreases. This in turn, increases the droplet size generated at the air orifice.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗
PubMed1994

Effect of detergent on alveolar particle clearance due to large tidal ventilation.

BACKGROUND: It has recently been shown that large tidal volume ventilation accelerates the alveolar clearance of insoluble particles and this may be related to accelerated surfactant evacuation from the alveolus into the airway. The aim of this study was to investigate if the effect of large tidal volume ventilation is modified in an experimental model of surfactant dysfunction. METHODS: Fluorescent latex particles of 0.63 microns diameter were administered in aerosol form to 30 rabbits during anaesthesia with thiopentone and mechanical ventilation. Six animals were killed immediately after aerosol administration in order to show the initial deposition of particles. Twenty four animals were divided into two groups and ventilated for three hours with either large tidal volume (mean tidal volume 30 ml/kg) or conventional ventilation (mean tidal volume 12.5 ml/kg). Six rabbits in each of the two groups were administered either the synthetic detergent dioctyl sodium sulphosuccinate in aerosol form or aerosolised vehicle. After the period of experimental ventilation the lungs were removed and dried in the expanded state. Particles in the alveolar region were counted with fluorescent microscopy in sections of the lung. RESULTS: Compared with the baseline group (mean (SD) 24.8 (9.9)) the count of residual alveolar particles was lower after large tidal volume ventilation in the absence of detergent aerosol (13.2 (6.5)). Particle count after large tidal volume ventilation and detergent treatment (23.3 (6.4)) was similar to that in the baseline group and to that in the groups exposed to conventional ventilation. CONCLUSIONS: The increase in alveolar clearance of insoluble particles caused by large tidal volume ventilation is inhibited by detergent aerosol. This might be due to reduced stability of the surfactant film after detergent aerosol.

Aerosols↗
PubMed1994

Tidal volume and alveolar clearance of insoluble particles.

We studied the effect of 3 h of large tidal volume ventilation on alveolar clearance of 0.63-micron fluorescent latex particles in rabbits during pentobarbital anesthesia. After particle deposition, six animals were killed as controls, six were subjected to large tidal volume ventilation with a peak pressure of 27 cmH2O, and six were subjected to conventional ventilation with a peak pressure of 11 cmH2O. Mean tidal volumes were 30.2 +/- 6.1 and 8.4 +/- 1.6 ml/kg in the large tidal volume and conventional groups, respectively. End-expiratory pressure was 2 cmH2O in all groups. Compliance decreased only after large tidal ventilation (P = 0.0036). Compared with controls the conventional ventilation group showed no alveolar clearance, but more particles were clustered within macrophages (P = 0.01). Compared with other groups the large tidal volume group had fewer alveolar particles (P = 0.0005), most of which were single particles. Accordingly, large tidal volumes enhance alveolar particle clearance, which is possibly related to distension-related evacuation of surfactant to proximal airways. Clearance may be due to accelerated motion of the particle-loaded macrophage in response to the fast film motion. Alternatively, single particles embedded in the surfactant film may be dragged by the fast-moving film toward the airways.

Animals↗
PubMed1994

Effect of inhaled budesonide on ozone-induced airway hyperresponsiveness and bronchoalveolar lavage cells in dogs.

Inhaled corticosteroids are known to reduce components of the airway inflammation characteristic of asthma and improve airway hyperresponsiveness. However, the effect of inhaled corticosteroids on ozone-induced airway responses is unknown. Eight dogs inhaled budesonide [2.74 +/- 0.25 (SE) mg/day] or lactose powder twice daily for 7 days before inhaling ozone (3 ppm for 30 min) or dry air. Acetylcholine airway responsiveness was measured before and 1 h after ozone, followed by a bronchoalveolar lavage (BAL). The response to acetylcholine was expressed as the concentration causing an increase in lung resistance of 5 cmH2O.l-1.s above baseline (acetylcholine provocation concentration). Budesonide pretreatment significantly attenuated the ozone-induced increase in pulmonary resistance (P = 0.003) and neutrophil influx into BAL (P = 0.001) and significantly reduced BAL eosinophils (P = 0.026). However, budesonide pretreatment had no significant effect on ozone-induced airway hyperresponsiveness. After budesonide, the acetylcholine provocative concentration fell from 5.96 mg/ml (%SE 1.46) before to 1.11 mg/ml (%SE 1.63) after ozone (P = 0.006). After lactose, the acetylcholine provocative concentration fell from 5.34 mg/ml (%SE 1.40) before to 0.50 mg/ml (%SE 1.85) after ozone (P = 0.001). Dry air inhalation did not cause airway hyperresponsiveness (P = 0.68). These results suggest that ozone-induced airway hyperresponsiveness is steroid resistant and that airway neutrophils or eosinophils are not important in its pathogenesis.

Acetylcholine↗
PubMed1992

Regional sensitivity of human airways to capsaicin-induced cough.

To examine the sensitivity of different parts of the human respiratory tract to a tussive and bronchoconstrictor stimulus, randomized, standardized single breaths of capsaicin aerosols were inhaled by nine healthy, nonsmoking subjects. A small droplet aerosol (3.2 microns MMD) was inhaled slowly (0.25 L/s), and a large droplet aerosol (5.2 microns MMD) was inhaled rapidly (1.0 L/s) to optimize differences in deposition, which were assessed after inhalation of 99mTc-DTPA aerosols with similar characteristics. Both capsaicin aerosols (zero to 256 microM) produced a concentration-dependent cough response. The geometric means (95% Cl) for the concentrations causing two coughs (cough threshold) were 2.3 microM (1.1 to 4.9) and 8.7 microM (3.1 to 24.5) (p less than 0.02), respectively, with the small and large droplet aerosols. The concentrations causing five coughs were 5.5 microM (3.0 to 10.0) with the small droplet aerosol and 29.5 microM (8.3 to 104.7) with the large droplet aerosol (p less than 0.02). In contrast, FEV1, measured 2 min after the largest concentration of capsaicin, was not significantly altered by any of the two capsaicin aerosols. In each subject, a similar dose was deposited in the larynx with both aerosols, whereas the dose deposited in intrapulmonary airways was 2.3 times larger with the small droplet aerosol. This study confirmed that slow inhalation of a small droplet aerosol produced a more peripheral airway deposition than did rapid inhalation of a large droplet aerosol. The small droplet aerosol was four times more potent, and capsaicin-sensitive sensory neurons mediating cough seem, therefore, to be present in human intrapulmonary airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Gas exchange during simulated airway secretion in the anaesthetized rabbit.

We wished to study the effect of airways secretion on gas exchange. Peripheral airway secretion was simulated in 9 rabbits by the continuous inhalation of nebulized isotonic saline, at a droplet size of about 3 microns. Intrapulmonary deposition of saline in the peripheral airways (83% in airways smaller than 0.5 mm) did not alter total inspiratory resistance (mean 5.4 kPa.l-1.s), but led to a decrease in compliance of the total respiratory system from 45.9 to 21.8 ml.kPa-1 after one hour of nebulization. Arterial oxygen tension decreased from 17.8 kPa to 12.1 and 6.9 kPa after 5 and 60 min of nebulization, respectively. PaCO2 was unaffected after 5 min (4.5 kPa) but increased to 7.0 kPa after 60 min of nebulization. Ventilation-perfusion relationships (VA/Q) showed a significant increase in perfusion of areas with low VA/Q ratios (from 0.7 to 6.3% of cardiac output) and in shunt (from 1.4 to 4.3%) after 5 min of nebulization. At the end of the experiment shunt was increased markedly to 29.7% of cardiac output whereas perfusion of low VA/Q regions remained at the same level (7.3%). The results from this animal model indicate that all gas exchange abnormalities known to occur in asthma can be reproduced without measurably increasing the resistance of the respiratory system.

Airway Resistance↗
PubMed1991

Regional sensitivity of the respiratory tract to stimuli causing cough and reflex bronchoconstriction.

Sensory nerves mediating cough and reflex bronchoconstriction have a non-uniform distribution in the respiratory tract. Afferent nerves originating in the laryngeal region differ from those of the intrapulmonary airways in their responsiveness to physical events in the breathing cycle and to chemical stimuli. Also, within each site afferents with separate characteristics are present. Studies in animals and human subjects have shown that the larynx and the carina are particularly sensitive to mechanical stimuli, whereas the intrapulmonary airways seem to be more sensitive to mediators and irritants. Based on recent data, the importance of the intrapulmonary airways to mediator/irritant-induced cough and reflex bronchoconstriction is emphasized. Inferentially, drugs inhibiting afferent neural activity arising in intrapulmonary airways would be a novel possibility in the treatment of cough and reflex bronchoconstriction.

Animals↗
PubMed1990

Antigen-induced dyspnea in Sprague Dawley rats. Effects of local treatment with anti-asthmatic drugs.

We wanted to study the effect of anti-asthma drugs on antigen-induced dyspnea in conscious Sprague Dawley (S.D.) rats. A line of dyspnea bred rats was produced, where all immunized animals respond with dyspnea when challenged with aerosolized ovalbumin (OA). The animals were immunized intraperitoneally (i.p.) with OA (10 micrograms) together with Al(OH)3 (100 mg) and challenged 2 to 3 weeks later with OA aerosol. We examined the effects of terbutaline (TERB), disodium cromoglycate (DSCG), atropine (ATRO), theophylline (THEO), a 5-HT receptor antagonist methysergide (METH), and two glucocorticosteroids (GCS) budesonide (BUD) and dexamethasone (DEX), on this response. The drugs were given locally either by intratracheal (i.t.) instillation or by aerosol. The rats were placed one by one in an air tight box and the breathing pattern was recorded. Parameters such as time of onset of dyspnea after end of challenge (elapsed time), duration and occurrence of dyspnea, were used to quantify the response. In the vehicle- treated group nearly all animals responded to OA with signs of dyspnea. TERB was the only drug effective when given as an aerosol, whereas when given i.t., also DEX and METH inhibited the dyspnea. Dyspnea is a serious response and can only be alleviated by the most effective anti-asthma drugs.

Animals↗