the wonderful effect of cupping therapy on bronchial asthma

Bronchial Asthma

☼     Definition: “Asthma is a chronic inflammatory disease of the bronchial tree characterized by hyper responsiveness to broncho-constricting stimuli with episodic air flow limitation that is reversible either spontaneously or with therapy “.

N.B: Another def. “Asthma is a lung disease with the following characteristics:

 1) Air way obstruction that is reversible either spontaneously or with drugs.

 2) Air way inflammation.

 3) Air way hyper responsiveness to a variety of stimuli.

☼     Etiology:

      – The aie of

Asthma are not fully understood. Asthma appears to be a multi factorial disorder with both Genetic and Environmental causes and is likely to be a Clinical Syndrome in which various precipitating factors result in similar clinical and pathologic manifestation. e.g., Childhood-onset atopic asthma, Adult-onset asthma in a middle aged ex-smoker without apparent allergies, and Asthma developing in the setting of occupational exposure to toluene di-isocyanate are likely to result from different cellular and molecular abnormalities despite their common characteristics of airway hyper responsiveness, air way inflammation, and variable air way obstruction.

      – Genetic factors: Asthma is familial. Recent genetic epidemiological studies have mapped a gene for asthma to a focus on chromosome 5, where numerous genes encoding inflammatory cytokines are located. Asthma is frequently associated with clinical manifestation of Atopy (Familial allergy to common allergens) and elevated serum total IgE concentration, but some evidence suggests that asthma and allergy may be inherited independently.

      – Epidemiological data suggest that exposure to certain environmental factors, especially early in life, such as allergens derived from dust mites, cats and other common environmental allergens may play a causal role in allergic sensitization and the development of atopic asthma. Passive exposure to environmental tobacco smoke appears to be a rich factor for the development of childhood asthma. A variety of chemicals encountered in the work place can cause asthma by mechanisms that apparently do not involve IgE-mediated hypersensitivity.

☼     Pathogenesis: The Eosinophil is a major effecter cell in asthmatic air way inflammation, but the Mast cell and T lymphocyte also play crucial roles.

      A- Mediators in the biology of Asthma: The inflammatory response in asthmatic airways is extremely complex. It is characterized by varying degrees of mononuclear cell and eosinophil infiltration, epithelial desquamation, mucus hyper secretion (airway plugging), smooth muscle hyperplasia, and airway remodeling with sub epithelial fibrosis.

1-Cytokines: -They are low molecular wt. protein molecules that are produced and secreted by all nucleated cells.

                                             -Cytokines regulate inflammation and the immune response.

-Principle cytokines implicated in asthma pathogenesis are: Interleukin-1B (IL-1B), IL5, IL3, IL4, and tumor necrosis factor-α (TNFα). They are produced by mast cells, T lymphocyte (TH2), macrophages and epithelial cells.

                                              -Cytokines have the following effects:

1) Recruit eosinophils to the airways and perpetuating eosinophilic inflammation in asthma.

2) Increase expression of adhesion molecule on endothelium which enhances inflammatory cell migration into the airway.

                                                            3) IL4 plays a key role in initiating IgE synthesis and TH2

lymphocyte development.

2-Histamine: -Histamine is primarily a product of synthesis from histidine in the        Golgi apparatus of mast cells and basophiles.

-It is released on activation of mast cells primarily through IgE-receptor interaction.

-Histamine has direct vaso-active and smooth muscle spasmogenic effects.

                        3-Arachidonic acid metabolites i.e., Lipid mediators (PGs and Leukotriens):

-They are produced by various inflammatory cell types, including mast cells, eosinophils, basophiles and macrophages.

                                                -PGD2 and PGF2α and leukotriens have the following effects:

                                                            1) Inflammation.                   2) Increased capillary permeability.

                                                            3) Bronchoconstriction.     4) Tissue injury.

                                                            4) Mucus secretion.

                        4) Contents of eosinophil granules:

                                                -These include 4 principle cationic proteins:

                                                            1) Major basic protein (MBP).

                                                            2) Eosinophilic cationic protein (ECP).

                                                            3) Eosinophil peroxidase (EPO).

                                                            4) Eosinophil-derived neurotoxin (EDN).

                                                -The ECP produce the following effects:

                                                            1) Cytotoxic to respiratory epithelium.

                                                            2) Promotes histamine release from mast cells.

                                                            3) Damage myelinated neurons.

            B-Airway smooth muscles:

-Bronchospasm remains an important component of asthma, particularly acute asthma.

-Smooth muscle is innervated by branches of both the parasympathetic (cholinergic) and sympathetic (adrenergic) nervous systems.

-The parasympathetic system is excitatory and vagal stimulation narrows the airways.

-The sympathetic system is inhibitory and stimulation of this system’s β-receptors results in smooth muscle relaxation.

            C-Bronchial hyper responsiveness:

-Asthma is characterized by hyper responsiveness. This is manifesting as an exaggerated constrictive response to a given amount of a non specific (Methacholine, Histamine) Or specific (Antigen) stimulation.

☼     Clinical features:

-The spectrum of disease severity: Some individuals with asthma may be entirely asymptomatic between attacks provoked by specific exposures. Other asthmatics may have nearly continuous symptoms and frequent severe attacks. Episodic exacerbation of asthma range from bothersome wheezing to life threatening attacks of respiratory failure.

-Asthma may present at any age including the extremes of life.

-The Cardinal symptoms of Asthma include: Episodic wheezing, Dyspnea, Chest tightness, Cough and Sputum production (sputum is small amount, sticky, white or clear usually, colored if infection, rarely profuse and frothy). Other presentation of asthma such as isolated persistent unexplained cough (Cough Variant Asthma), Or Exertional chest tightness Or Dyspnea.

N.B.: Of particular importance in diagnosis of asthma is the Periodicity of symptoms.

-Provoking Factors:

            1) Allergy: # Over 90% of childhood asthmatic and 50% of adult are atopic.

# Episodes of wheezing and Dyspnea provoked by inhalation of airborn allergens.

                        2) Infection: Viral infection

                        3) Air pollution                                      4) Smoking

                        5) Psychological factors                         6) Gastro-esophageal reflux

                        6) Exercise (exercise induced asthma)

                        7) Aspirin induced asthma: charact. by Asthma + Nasal polyposis + Asp. Sensitivity.

           

N.B.: Atopic individuals: are people who have the inherited ability to produce Igs and Abs in response to allergenic stimulation

-Signs:

ü  The characteristic clinical finding in asthmatic patient is wheeze. Wheezing is caused by high velocity, turbulent airflow through narrowed airways; it is usually present during expiration, although it may be present during inspiration as well. Wheezing is typically Polyphonic, indicating their origin from many separate airways (Non-uniformity of airflow). Wheezing may be absent in very mild and very severe airway obstruction.

ü  Clinical signs of Rhinitis, Sinusitis and Nasal polyps are seen more commonly in patients with asthma.

ü  Patients with asthma may have entirely Normal physical examination In-between Exacerbations.

-Acute Severe Asthma:

ü  Acute severe attacks represent progression of an attack of Bronchospasm to the point where the patient is breathless at rest and has signs of cardiac stress.

ü  Symptoms:

                                                                                 i.            Increasing breathlessness.

                                                                               ii.            Difficulty in talking or inability to do anything other than breathing.

                                                                              iii.            Anxiety

                                                                             iv.            The patient sits up in bed and chair

                                                                               v.            Wheezes are audible without stethoscope and the chest is is visibly over inflated.

                                                                             vi.            Sweating profuse in severe attacks.

                                                                            vii.            Cough is usually not prominent and is almost never productive in the acute episodes. Production of sputum can be taken as an encouraging sign of recovery.

                                                                          viii.            Tachycardia.

                                                                             ix.            Pulsus paradoxus.

                                                                               x.            Arterial blood gases show Hypoxemia and hypercapnia initially. Hypercapnia only occurring in the pre-terminal stages of an attack.

☼     Investigations:

A.     Pulmonary function tests: pulmonary function tests are important for Confirming the diagnosis, Establishing the severity of the disease, and Monitoring the response to therapy.

                                                                                 i.            Spirometry: The diagnosis of asthma is usually confirmed by objective demonstration of airway obstruction by Spirometry, and evidence of significant improvement in the 1 sec. forced expiratory volume (FEV1) after bronchodilator administration.

Pattern of airflow limitation are:

            àReduction in the FEV1/FVC ratio.

            àReduced FEV1 and FVC.

            àRelatively greater reduction in FEV1 than FVC.

Post bronchodilator increase in FEV1 of 15-20% is evidence of reversible airway obstruction.

                                                                               ii.            Peak Expiratory Flow (PEF):

-Measurements of PEF before and after a bronchodilator may be useful for detecting reversible airway obstruction.

-Asthma is characterized by increased variability in PEF.

-PEF is usually lowest in the early morning and highest in the late afternoon.

-A variability in PEF of at least 20% is significant in diagnosis of asthma.

                                                                              iii.            Lung volumes: Residual volume (RV), Functional residual capacity (FRC), and Total lung capacity may increase in acute asthmatic episodes.

                                                                             iv.            Diffusing Lung Capacity: Usually Normal in asthma

                                                                               v.            Arterial Blood Gases:

-Typically Normal in patients with chronic stable asthma.

-During an acute episode Hypoxemia is often present + Hypercapnia.

-Arterial PCO2is typically reduced owing to hyperventilation.

-Severe obstruction à Arterial PCO2 rise

B.     Radiography:

-Because the chest radiograph is generally un remarkable in patients with uncomplicated asthma, it is used primarily to exclude other causes of respiratory symptoms.

-Non-Specific radiographic findings such as Over inflation, Prominent hilar vessels, and increased broncho-vascular markings (Dirty lung appearance).

-Over inflation has been reported in asthmatics with severe disease, chronic, persistent, rather than intermittent, and during acute exacerbation.

C.     Electrocardiography:

-Asthma in remission is usually not associated with ECG abnormalities.

-During an acute exacerbation several abnormalities can occur including sinus tachycardia, P-pulmonale, right axis deviation, right bundle branch block, right ventricular strain and a variety of arrhythmias.

-ECG also helpful in excluding cardiac disease as a cause of chest symptoms.

D.     Blood tests:

-Eosinophiles may be seen in peripheral blood in both allergic and non-allergic asthmatics.

-Elevated total IgE serum level are frequently seen in allergic patients but the findings are not specific for asthma.

E.      Sputum examination:

-Sputum eosinophilia is more charecterstically found in asthmatics than in patients with COPD.

-Neutrophiles are found more often in patients with an acute exacerbation of chronic bronchitis.

-Sputum eosinophilia can be seen in both disorders.

F.      Allergy tests:

-Tests to determine whether the patient is allergic and to investigate the role of specific allergens as a cause of asthma.

-Skin Prick test is performed by putting a drop of allergen on the skin, usually the front surface of the forearm, and lifting the skin lightly through the drop with the point of an intra-dermal needle, the test should be read about 15-20 minutes later. A wheel is a positive result.

G.     Bronchial Challenge testing:

-Bronchial hyper responsiveness may be detected by broncho provocation tests with an inhaled pharmacologic bronchoconstrictor such as histamine or methacholine.

-N.B Airway responsiveness is measured using increasing doses of a bronchoconstrictive stimulus, and then quantitating the decline in lung function caused by the stimulus. The most common pharmacologic stimuli are histamine or methacholine, increasing bronchoconstrictive doses of histamine or methacholine are administered, and when the patient’s FEV1 decreases by 20% from its initial value, the test is terminated. The dose at which this drop occurs is called the Provocative dose or PD20. Individuals that manifest a PD20 at a low dose of stimulus are said to have increased airway responsiveness and are hyper responsive to the inhaled agent.

☼     Differential Diagnosis:

1-      COPD: Chronic bronchitis, Emphysema.

2-      Laryngeal dysfunction.

3-      Congestive feature failure.

4-      Pulmonary eosinophilia.

5-      Pulmonary embolism.

6-      Chronic sinusitis and Gastro esophageal reflux.

7-      Acute bronchiolitis.

8-      Localized anatomic lesions obstructing airway, e.g., tumors, FB.

☼     Management of Asthma:

1-      Non pharmacologic therapy:

-Non pharmacologic management strategies including patient education & avoidance of asthma triggers.

·         Education: the goal of asthma education is to improve patient understanding of the disease and its management and consequently to improve adherence to treatment recommendations.

·         Environmental control: Avoidance of aeroallergens, viral respiratory pathogens, air pollution and certain drugs (beta blockers, aspirin) can prevent exacerbation, reduce the need for drug treatment and decrease utilization of emergency facilities.

·         Influenza vaccination has been shown to reduce the incidence of upper respiratory illneses in people of all ages, thus it would decrease the incidence of exacerbation of asthma.

·         Allergen immunotherapy also appears to be of benefit in highly selected patients with defined allergic triggers. As a rule, patients who have many allergic triggers tend to benefit less from immunotherapy than those with a single trigger.

2-      Pharmacological Management: (Asthma Medications)

-Drugs available for treatment of asthma are:

I.  Bronchodilators:

a)      β-adrenergic agents:

                                                                     i.      Non selective β-adrenergic agonists: stimulate both α & β receptors. i.e., Adrenaline, Nor-Adrenaline, Ephedrine, Isoproternol ( onset <5 min., duration 2-3 hrs ).

                                                                   ii.      Selective β2-adrenergic agonists:

a.Short acting β2-agonists:

-i.e., Albuterol, Terbutaline, Salbutamol.

-Method of administration:

üOral ( tablets, suspension )

üInhalation: MDI, Solution (Nebulizer), Dry powder.

-Inhaled short acting β2-agonists are the drugs of Choice to provide immediate relief of symptoms and acute air flow obstruction caused by asthma. By stimulating bronchial smooth muscle β-adrenergic receptors, these agents cause smooth muscle relaxation and bronchodilatation within 10-15 min. of administration. The duration of action of these agents is 4-6 hrs. Oral preparations are available for patients who can not use inhalers.

-Side-effects: Tremors, Palpitations, Anxiety, and Hypokalemia.

b.Long acting and sustained release β2-agonists:

-Long acting inhaled β2-agonists (Salmetreol, Formeterol) which have Onset 1-2 hrs. And at least a Duration of 12 hrs. of action. These agents are not recommended for the short term relief of acute symptoms, but used as maintenance medications and should be given twice daily on a long term basis.

-Oral sustained release β2-agonists (Albuterol) have one advantage of BID oral administration.

b)      Theophylline:

-It has the following properties: (Advantages)

üWeak bronchodilator àby inhibiting the Phospho-di-esterase enzyme (PDE).

üAnti-inflammatory effect.

üEnhanced muco-ciliary clearance.

üImproved diaphragmatic muscle contractility.

-Disadvantages include:

      Potential GIT, CNS, and CVS toxicity.

      The need to monitor serum levels due to low therapeutic to toxic ratio.

      Drug interaction with erythromycin, cimetedine, and ciprofloxacin.

-Route of administration:

üOral à sustained release tab., syrup.

üParenteral à I.V, I.M.

üRectal à suppositories.

-Therapeutic serum level à 10-20 μg/ml.

c)      Anti-cholinergic agents: i.e., Ipratropium bromide

-Anti-cholinergic agents induce airway smooth muscle relaxation by blocking muscarinic receptors on airway smooth muscle thus inhibiting vagally mediated cholinergic tone.

-They have a slower onset of action than β-agonists; the duration of their activity is more prolonged, usually lasting for 6-8 hrs.

-They are often given in combination with β-agonists in the management of severe acute asthma.

-Method of administration:

üInhalation à MDI, solution (Nebulizer).

II.     Anti-inflammatory agents:

a)      Corticosteroids:

-Glucocorticoids are the most effective agents available for treating moderate to severe asthma. Steroid efficacy is generally attributed to anti-inflammatory effects.

-Glucocorticoids are available for systemic or inhalation use.

-Inhaled glucocorticoids include: Beclomethasone dipropionate, Budesonide, Fluticasone.

-Systemic glucocorticoids include:

üOral preparations à Prednisolone, prednisone, cortisone, betamethasone.

üParentral preparations à Hydrocortisone, methyl prednisolone, betamethasone, dexamethasone.

-Side effects include:

üSystemic à Adrenal suppression, Osteoporosis, Hypertension, DM, Myopathy, Growth suppression, and Psychiatric reaction.

üLocal à Oral Candidiasis and Dysphonia.

b)      Cromolyn sodium and Nedocromyl sodium:

-They reduce bronchial responsiveness to inhaled allergens, reduce airway inflammation and prevent asthma symptoms and exacerbation.

-They appear to inhibit the release of bronchoconstricting and pro inflammatory mediators and cytokines by mast cells, eosinophils and other cells important in the pathophysiology of asthma.

c)      Leukotriene modifiers:

-Zileuton (a leukotriene synthesis inhibitor) and Zafirlukast (a leukotriene receptor antagonist) are oral medications which had recently approved for the treatment of asthma.

-These agents results in persistent bronchodilatation, reduced asthma symptoms, reduced medication use, reduced awakening from sleep at night, diminished need for prednisone therapy.

-Pharmacological Management of Asthma can be divided into:

I.  Long term management:

# Formulation of long term management plan for a patient with asthma requires the following:

1.Assessment of the frequency and severity of asthma symptoms.

2.The frequency of nocturnal symptoms interfering with sleep.

3.The degree of disruption of school or work by asthma.

4.The number of hospitalization or emergency department visits for asthma attacks.

# Peak expiratory flow rate (PEFR) or spirometry should be performed to assess the severity of airflow obstruction.

# Asthma therapy should be tailored to the severity of asthma for each individual patient.

# Treatment regimens based on classification of asthma severity are:

1)      Mild intermittent asthma:

-Clinical features: (Cough, wheezing, dyspnea)

v  Daytime symptoms ≤ 2 times/wk.

v  Nocturnal symptoms ≤ 2 times/mo.

v  Peak flow or FEV1 ≥ 80 % predicted (when asymptomatic).

-Therapy:

v  Short acting β-agonist à On an as-need basis (1-2 buffs by MDI).

2)      Mild persistent asthma:

-Clinical features:

v  Daytime symptoms > 2 times/wk. but not daily.

v  Nocturnal symptoms > 2 times/mo.

v  Peak flow or FEV1 ≥ 80 % predicted.

-Therapy:

v  Short acting β-agonist à as needed, low dose.

v  Long acting β-agonist. OR

v  Cromolyn sodium. OR

v  Inhaled glucocorticoids. OR

v  Leukotriene modifiers.

3)      Moderate persistent asthma:

- Clinical features:

v  Daytime symptoms à Daily.

v  Nocturnal symptoms > 1 times/wk.

v  Peak flow or FEV1 > 60 % to < 80 % predicted.

- Therapy:

v  Short acting β-agonist à as needed, medium to high dose.

v  Long acting β-agonist. PLUS

v  Inhaled glucocorticoids. OR

v  Sustained release Theophylline.

4)      Severe persistent asthma:

- Clinical features:

v  Daytime symptoms à Continuous.

v  Nocturnal symptoms à Frequent.

v  Peak flow or FEV1 ≤ 60 % predicted.

- Therapy:

v  Short acting β-agonist à as needed, high dose.

v  Long acting β-agonist.

v  Inhaled glucocorticoids.

v  Sustained release Theophylline.

# Patients not controlled with inhaled glucocorticoids and one or more long acting bronchodilator are often considered candidates for systemic glucocorticoid therapy 0.5 mg/kg/day for 8-21 days, followed by a tapering course to the lowest dose that maintain control.

II.     Management of Acute Exacerbations (Status Asthmaticus):

# Acute asthma exacerbations may be Fatal, and patients presents with this condition must be treated aggressively and monitored with great care.

# Initial assessment of a patient with an acute exacerbation should include:

1.History à Focusing on Previous asthma hospitalization, intubations, Steroid use, and symptoms suggesting infection.

2.Physical Examination à focusing on Vital signs, Breath sounds, Use of accessory muscles, and cyanosis.

3.Measurement of PEFR or FEV1.

4.Oximetry.

5.Arterial bl. Gases à in more severe cases.

# Standard Therapies:

1)      β-agonists

à Inhaled Albuterol , Epinephrine by Nebulizer or MDI.

2)      Corticosteroids

à Prednisone, Methyl prednisolone.

à High dose I.V. (Methyl prednisolone 60-120 mg every 6 hrs.).

3)      Oxygen

à Titrated to achieve values of 92-94 %.

4)      Anti-Cholinergics à Ipratropium bromide.

5)      Theophylline

à I.V. 5 mg/kg over 30 min. Loading dose.

à 0.5 mg/kg/hr. Maintenance dose.

6)      Antibiotics à When needed.

N.B The patient with asthma where FEV1 & PEFR not increase to > 40 % of the predicted value with treatment, where PaCo2 is within normal range in the presence of severe airflow obstruction, or who develop life threatening conditions such as pneumothorax or pneumomediastinum should be admitted to hospital where they can be closely monitored (Acute severe asthma).

Cupping effect on chronic bronchitis and bronchial asthma

The nitric oxide “released by the action of cupping” stimulates blood circulation in the lungs, which helps to decrease contraction of the muscles of the airways and reduce inflammation of the lining of the airways, which facilitate the air flow in and out.

cupping working on reducing the level of histamine, which reduces the bronchial sensitivity to external stimuli

cupping working on reducing secretions that cause airway obstruction and increased movement of the cilia and out secretions

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Experiences and scientific results

The results of  bronchial asthma with cupping were good results and may last up to 6 sessions.