Methacholine test

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The methacholine (methacholine provocation test, English Methacholine Challenge Test ) is a nonspecific, inhalation challenge test , the in pneumology and allergy to measure bronchial obstruction z and bronchial hyperresponsiveness. B. is used in bronchial asthma .

clinic

indication

The origin of bronchial asthma is a hypersensitive ( hyperreactive ) bronchial system . Various stimuli can cause shortness of breath or a cough in the presence of a hyperreactive bronchial system . For the diagnosis of bronchial asthma, the measurement of the hypersensitivity of the bronchi is crucial. The methacholine test is used for this. Methacholine is a drug that, depending on the dose , can cause bronchial constriction, even in healthy subjects.

Preparation of the methacholine chloride provocation doses

In Germany, methacholine chloride is sold by Aristo Pharma GmbH under the trade name Provokit 0.33% inhalation solution (powder and solvent). Provokit contains in a 10 ml vial (red) with powder: 33 mg methacholine chloride and, as excipients, disodium hydrogen phosphate-2-water and sodium dihydrogen phosphate-1-water , in a vial (blue) with solvent: water for injections .
In Canada and the USA , methacholine chloride solutions are available in various concentrations under the trade name Provocholine . The finished solutions are also often produced in pharmacies according to prescriptions and defects . In the case of the above-mentioned commercial preparations, the powder and solvent are separate and can be prepared yourself if necessary.

Performing the methacholine test and evaluating the results

The methacholine test is associated with a large amount of equipment and requires appropriate specialist knowledge. It is therefore usually carried out in a specialized clinical laboratory.

First of all, lung function is measured using body plethysmography under resting conditions . This large pulmonary function test in a pressure-stable glass cabin allows, in particular, the determination of the airway resistance independent of the volunteer's cooperation. In addition, overinflation of the lungs (e.g. pulmonary emphysema ) or a reduction in the size of the lung tissue (e.g. pulmonary fibrosis ) can be detected. This is followed by inhalation of the carrier solution in order to determine a blank value. Significant changes in lung function can already be recorded here in highly reactive patients. In such a case, further inhalative provocation is not necessary. This is followed by the gradual - with increasing dosage - inhalative application of the bronchoconstrictive substance methacholine chloride to the patient using a nebulizer. Between the individual stages (usually five) is the so called forced expiratory volume (engl. Forced Expiratory Volume per 1 second , FEV 1 ) are measured and a dose-response relationship created.

At the end of the examination, the patient is given a drug, usually salbutamol (Ventolin ® ), administered by inhalation to remove the bronchial constriction (spasmolysis test). As soon as the initial lung function is reached again, the methacholine test is considered to have ended.

pharmacology

Interactions with other drugs

Since various drugs can influence the bronchial system and thus the examination results, these should be paused if possible. However, this must always be done after consulting the attending physician. The following drugs (with a waiting period in hours or days) are particularly affected:

Precautions

For provocation tests with methacholine chloride, the same precautionary measures apply that are fundamentally necessary in lung function laboratories. The staff must be familiar with the treatment of airway obstruction, including the asthma attack . If necessary, it must be possible to administer oxygen and inhaled β 2 -sympathomimetics . A doctor with experience in emergency medicine must be available at all times. The methacholine test may only be performed once on a patient in a 24-hour period.

Use during pregnancy and breastfeeding

  • The methacholine test should not be performed during pregnancy. Effects on intrauterine development in animal studies have not been adequately studied and there is no experience in pregnant women.
  • It is not known whether methacholine chloride is excreted in breast milk. Use during breastfeeding is therefore contraindicated .

Contraindications

The methacholine test must not be carried out if:

Special care is also needed when in the history of a status asthmaticus or anaphylactic shock is eruierbar.

Side effects

The following undesirable effects may occur after inhalation of methacholine chloride :

  • Rare: irritation in the throat area, pruritus (itching), dyspnea (difficulty breathing), cough, wheezing ( pulmonary noise ), tiredness, drowsiness, dizziness, headache, nausea, flushing, tightness in the chest, hypersalivation (increased salivation), waste diastolic blood pressure, tachycardia (increased pulse) and bitter taste.
  • In individual cases: Pneumothorax (accumulation of air in the pleural space), diarrhea (diarrhea), gastrointestinal complaints and increased urination.

Pharmacodynamics and pharmacokinetics

Methacholine with the ATC code V04CX11 is a muscarinic receptor - agonist , the slower by cholinesterases is mined as acetylcholine . It is a direct cholinergic , parasympathomimetic bronchoconstrictor that works by stimulating the vagus nerve .

Acute toxicity: Studies have shown an LD 50 of 15 mg / kg in mice after iv application of methacholine chloride . In the rat, the LD 50 after oral administration is 750 mg / kg. Methacholine chloride may only be used as an aerosol for inhalation. Symptoms of accidental poisoning can include vomiting, nausea, hypotension and unconsciousness. In the case of severe cardiovascular or bronchoconstrictor symptoms, atropine sulfate can be administered as an antidote either intravenously or intramuscularly. Atropine is a parasympatholytic and thus inhibits the muscarinic effects of methacholine through competitive inhibition of the acetylcholine receptors in the synaptic cleft.

Veterinary medicine

Chronic obstructive pulmonary diseases are widespread in the temperate horse population. Initial studies show that bronchial hyperreactivity plays an important role in the pathophysiology of these diseases.

Chemistry of methacholine chloride

Methacholine chloride , a β-methyl derivative of acetylcholine from the group of quaternary ammonium compounds , is used for the provocation test . The chemical name according to IUPAC is: 2-acetoxypropyltrimethylammonium chloride. They are colorless crystals or white, crystalline powder, which are very easily soluble in water, easily soluble in 96% ethanol and insoluble in diethyl ether . The melting point is 172-173 ° C. The molecular formula is C 8 H 18 ClNO 2 , CAS Number 62-51-1 and a molar mass of 195.69  g · mol -1 . Methacholine chloride is very hygroscopic .

Historical development

"Alexander and paddock first described in 1921 systematically triggering asthma attacks in humans by injection of pilocarpine . This was preceded by animal experiments by Dale and Laidlow in 1910. Tiffenau et al. (1945) used acetylcholine and curry introduced histamine as a provocation substance in 1946 . A wide variety of bronchoconstrictive agents were used later. Traditionally, histamine was used most often as a well-known mediator of natural, allergic-induced bronchoconstriction. Because of the not inconsiderable systemic side effects of this substance, cholinergics such as methacholine or carbachol , which are more effective for longer periods of time, are used today . The introduction of asthma provocation tests into clinical diagnostics was only possible when measuring methods for objectifying the induced changes in lung function were available. In 1946, Dautrebande and Phillipot used the vital capacity as a success parameter in the first described inhalative provocation test with carbachol . However, measurement parameters such as FEV 1 or s R AW , which are viewed as a more valid measure of the obstruction, also established themselves later . The use of an aerosol reservoir, initially in the form of a spirometer bell (Tiffenau) and later with the help of a simple plastic bag, was a major step towards a standardizable, diagnostic method . In this way, the amount of substance applied could be determined from the volume of the inhaled aerosol . "

- from : the bronchial provocation test with methacholine; Standardization and evaluation of a measurement protocol for routine examinations, dissertation by Johannes G Ammon from Stuttgart, 1995, p. 9

See also

literature

General

  • M. Classen, V. Diehl, K. Kochsiek: Internal medicine . Urban & Schwarzenberg, Munich a. a. 1991, ISBN 3-541-11671-4 , pp. 1087-1166.
  • Joachim Saloga (ed.): Allergology manual. Basics and clinical practice . With the collaboration of Peter Angerer. Schattauer, Stuttgart a. a. 2006, ISBN 3-7945-1972-8 .
  • Patent US6462090 : Formulations for detecting asthma. ‌
  • E. Gonsior, M. Henzgen, RA Jörres, RF Kroidl, R. Merget, F.-W. Riffelmann, G. Wallenstein: Guideline for the implementation of bronchial provocation tests with allergens - German Society for Allergology and Clinical Immunology and German Society for Pneumology. In: Pneumologie , 56, p. 187, doi: 10.1055 / s-2002-20553 .
  • AARC Clinical Practice Guideline Methacholine Challenge Testing . In: Respiratory Care , 46 (5), 2001, pp. 523-530.

Studies

  • H. Huber, R. Lauschner et al. a .: Randomized double-blind study (third place blinded) to investigate the effectiveness and side effects of methacholine in the non-specific bronchial provocation test. In: Pneumologie , 54, pp. 99-103, doi: 10.1055 / s-2000-9080
  • HC Siersted, CM Walker, AD O'Shaughnessy, AR Willan, EM Wiecek, MR Sears: Comparison of two standardized methods of methacholine inhalation challenge in young adults . In: European Respiratory Journal . tape 15 , no. 1 , 2000, pp. 181–184 ( ersjournals.com [PDF; accessed February 17, 2011]).
  • Nathan D. Allen, Beth E. Davis, Thomas S. Hurst, Donald W. Cockcroft: Difference Between Dosimeter and Tidal Breathing Methacholine Challenge . In: Chest . tape 128 , no. 6 , November 1, 2005, pp. 4018-4023 , doi : 10.1378 / chest.128.6.4018 .
  • Birgitta Schmekel, Hans Hedenström, Mary Kämpe, Lars Lagerstrand, Gunnemar Stalenheim, Per Wollmer, Göran Hedenstierna: The Bronchial Response, but not the Pulmonary Response to Inhaled Methacholine Is Dependent on the Aerosol Deposition Pattern . In: Chest . tape 106 , no. 6 , November 1, 1994, pp. 1781–1787 , doi : 10.1378 / chest.106.6.1781 .
  • Guidelines for Methacholine and Exercise Challenge Testing - 1999 . In: Am. J. Respir. Crit. Care Med. Volume 161 , no. 1 , 2000, pp. 309-329 ( HTML [accessed February 17, 2011]).
  • CB Sherman, DG Kern, RW Corwin, B. Andrus: A clinical and structural comparison of industrial methacholine and provocholine . In: Chest . tape 105 , no. 4 , March 1, 1994, pp. 1095-1097 , doi : 10.1378 / chest.105.4.1095 .
  • Jeffrey M Haynes: A positive methacholine challenge test in the absence of symptoms . In: Respiratory Care . tape 52 , no. 6 , 2007, p. 759-762 , PMID 17521467 ( rcjournal.com [PDF; accessed February 17, 2011]).
  • A. Dierkes-Globisch, A. Globisch u. a .: Validity of inhalation provocation tests to determine the non-specific bronchial reactivity - comparison of different methods. In: Pneumology. 56, p. 230, doi: 10.1055 / s-2002-25071 .

Web links

Wiktionary: bronchoconstriction  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b c d Provokit specialist information . August 18, 2007.
  2. ↑ Stability of methacholine chloride solutions under different storage conditions over a 9 month period. (PDF; 186 kB). In: Eur Respir J. 11, 1998, pp. 946-948.
  3. ↑ Validity of body plethysmography and spirometry for recording bronchial hyperreactivity with methacholine (PDF; 100 kB) Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Bochum
  4. ↑ Comparison of a reservoir (Pari Provotest II) and dosimeter (ATS) method for testing bronchial hyperreactivity with methacholine (PDF; 81 kB) Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Bochum
  5. ↑ Investigation of the waiting interval of montelukast before inhalative bronchial allergen challenge . In: Pneumology . tape 57 , no. 8 , 2003, p. 429-432 , doi : 10.1055 / s-2003-41542 .
  6. ↑ Andreas Richter: Changes in bronchial hyperreactivity under need-based versus regular β2-agonistic therapy. 2005 (Dissertation, Heinrich Heine University, Düsseldorf 2005; DNB [PDF])
  7. ^ WM Alberts, PR Ferguson, JW Ramsdell: Preparation and handling of methacholine chloride testing solutions. Effect of the hygroscopic properties of methacholine . In: The American Review of Respiratory Disease . tape 127 , no. 3 , February 1983, p. 350-351 , PMID 6338784 .