Bronchial asthma

Asthma is a chronic inflammatory disorder of the airways, associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night and in the early morning, usually associated with widespread but variable airflow obstruction within the lung that is often reversible, either spontaneously or with treatment.

*Based on– Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 666

Asthma is a chronic inflammatory condition of respiratory tract presenting with features of reversible airflow limitations.

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 95

Asthma generally grouped into 3 types

1. Intermittent asthma
2. Persistent asthma
   • Mild persistent asthma
   • Moderater persistent asthma
   • Severe persistent asthma
3. Special variant asthma
   • Seasonal asthma
   • Exercise induced asthma
   • Drug induced asthma
   • Cough variant asthma
   • Occupational asthma

Any of these types may develop acute exacerbation.

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 96

When asthma symptoms become cumbersome, following exposure to certain situations are called special variant asthma.

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 96

As follows:

Intrinsic asthma (non atopic or late onset asthma):

• When no causative agent can be identified.
• It is not allergic, usually begins after the age of 30 years, tends to be more continuous and more severe.

Extrinsic asthma (atopic or early onset asthma):

• When a definite external cause is present.
• There is history of allergy to dust, mite, animal danders, pollens, fungi, etc.
• It occurs commonly in childhood and usually shows seasonal variations.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 64

It is defined as “severe acute persistent attack of asthma without any remission in between and not controlled by conventional bronchodilator”. Previously it was called status asthmaticus.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 64

There is no breath sound heard on auscultation. This is a sign of life-threatening asthma.

* Pre-exam preparation for medicine, HN Sarker

Three cardinal features:

• Airflow limitation – it is usually reversible spontaneously or with treatment
• Airway hyper-responsiveness – airway is hyper-responsive to a wide range of nonspecific stimuli like exercise, cold air
• Airway inflammation – there is inflammation of the bronchi with infiltration of eosinophils, T cells and mast cells. Also there is plasma exudation, edema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage

(In chronic asthma, inflammation may lead to irreversible airflow limitation due to airway wall remodeling, involving the large and small airways with mucus impaction.)

* Long Cases in Clinical Medicine, ABM Abdullah Page: 62

Pathophysiological events are

• Exaggerated spasm of bronchial smooth muscles
• Vasodilation with increased permeability and swelling of wall of airway
• Profuse mucous secretion
• Vagal stimulation

The net pathological consequences are – Recurrent airway

• Inflammation
• Airflow obstruction/narrowing

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 95

Common triggering factors

Pollens, dust, smoke, aerosol spray, viral catarrh, NSAID, foods, house dust, mites, cockroach and many others.

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 95

The common causes of occupational asthma are:

• Isocyanates
• Flour and grain dust
• Colophony and fluxes
• Latex
• Animals
• Aldehydes
• Wood dust.

* Pre-exam preparation for medicine, HN Sarker

Typical symptoms include recurrent episodes of

• wheeze,
• chest tightness (older children),
• breathlessness and
• cough

which display a diurnal pattern, with symptoms and lung function being worse in the early morning.

* Pre-exam preparation for medicine, HN Sarker; Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 96

The features of acute severe asthma are:

• Respiratory rate is ≥ 25/min
• Heart rate is ≥ 110/min
• Inability to complete sentences in 1 breath
• PEF 33%–50% predicted (< 200 L/min).

* Pre-exam preparation for medicine, HN Sarker

Note:

Pulsus paradoxus may be found in up to 45% of acute severe asthma.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 64

As follows:

• Profound exhaustion
• Cyanosis
• Silent chest
• Feeble respiratory effort
• Bradycardia or arrhythmia
• Hypotension

Note:

On examination:

• PEFR < 33% of predicted (< 100 L/min)
• Blood gas analysis – SpO₂  < 92% or PaO₂  <8 kPa (60 mm Hg) even with O₂
• Normal or raised PaCO₂  (> 6 kPa) and low or falling blood pH.
• If a patient has raised PaCO₂ and/or requires mechanical ventilation with raised inflation pressure, it is called near fatal asthma.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 64; Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 96; Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 671

See on dyspnea from presenting problems of respiratory system

As follows:

Stridor is a high pitched, loud sound produced by partial obstruction of major airways like larynx, trachea or large bronchi. It is heard both in inspiration and expiration. Causes are— foreign body in larynx or trachea, laryngeal edema (angioedema), laryngeal tumor, vocal cord palsy due to recurrent laryngeal nerve paralysis, tumor, infection (e.g. epiglottitis, acute laryngitis, diphtheria, whooping cough) or inflammation, paratracheal and subcarinal lymphadenopathy pressing over the main bronchi, laryngismus stridulus in tetany. This indicates an emergency condition.

Wheezes are a musical sound heard from a distance, due to small airways obstruction. High pitched wheezes are produced by obstruction in smaller bronchi and low pitched wheezes are produced in larger bronchi. It is present both during inspiration and expiration but prominent during expiration. Wheezes are caused by severe bronchial asthma, chronic bronchitis or COPD or airways obstruction by a foreign body or tumor.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 69

Key distinguishing feature is the reversibility test. Bronchial asthma is fully reversible with use of bronchodilator which leads to >15% and 200 mL increase in FEV1 (except in severe persistent asthma). COPD is not fully reversible and the increase in FEV1 after bronchodilator is < 15%. The differences between bronchial asthma and COPD are:

* Long Cases in Clinical Medicine, ABM Abdullah Page: 68

Examination of chest

• Inspection : Hyperinflation of chest, suprasternal, subcostal & intercostal recession
• Percussion : Hyper resonant
• Auscultation : Vesicular breath sound with prolonged expiration, rhonchi

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 96

Peak expiratory flow rate is the bedside test of asthama.

* Pre-exam preparation for medicine, HN Sarker

Reversibility test is to see the reversibility of airflow obstruction in obstructive lung diseases.

* Pre-exam preparation for medicine, HN Sarker

Reversibility test is done by measuring forced expiratory volume in 1 second before and 20 minutes after administration of 200–400 μg of inhaled salbutamol or after 2 weeks of a trial of corticosteroids (e.g. 30 mg prednisolon daily for 2 weeks).

* Pre-exam preparation for medicine, HN Sarker

When FEV1 ≥ 15% (or 200 mL) increase following administration of a bronchodilator /trial of corticosteroids.

* Pre-exam preparation for medicine, HN Sarker

There is no single satisfactory diagnostic test for all patients with asthma.

1. Lung function tests
   • Peak expiratory flow rate (PEFR)
     • The diurnal variation in PEFR is a good measure of asthma activity.
     • It helps in the longer-term assessment of the patient’s disease and its response to treatment.
   • Spirometry
     • Asthma can be diagnosed by demonstrating a greater than 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator.
   • The carbon monoxide (CO) transfer test is normal in asthma.
2. Exercise tests
   • These have been widely used in the diagnosis of asthma in children.
3. Blood gas analysis
   • PaO₂ (reduced )and PaCO₂ (raised or normal).
4. CBC and sputum for eosinophil count
   • Patients with asthma sometimes have increased numbers of eosinophils in peripheral blood (>0.4 × 109/L) but sputum eosinophilia is a more specific diagnostic finding.
5. Chest X-ray
   • There are no diagnostic features of asthma on the chest X-ray, although overinflation is characteristic during an acute episode or in chronic severe disease.
   • A chest X-ray may be helpful in excluding a pneumothorax, which can occur as a complication, or in detecting the pulmonary infiltrates associated with allergic bronchopulmonary aspergillosis.
6. Histamine or methacholine bronchial provocation test
   • This test indicates the presence of AHR (airway hyperresponsiveness), a feature found in most asthmatics, and can be particularly useful in investigating those patients whose main symptom is cough.
   • The test should not be performed on individuals who have poor lung function (FEV1 <1.5 L) or a history of ‘brittle’ asthma. In children, it is often easier to carry out controlled exercise testing as a measure of bronchial hyper-responsiveness.
7. Trial of corticosteroids
   • A substantial improvement in FEV1 (>15%) confirms the presence of a reversible element and indicates that the administration of inhaled steroids will prove beneficial to the patient.
8. Exhaled nitric oxide
   • This test is a measure of airway inflammation and an index of corticosteroid response; it used to assess the efficacy of corticosteroids.
9. Skin-prick test
   • To help identify allergic trigger factors.
10. Allergen provocation tests
    • Required when investigating patients with suspected occupational asthma, but not in ordinary asthma.

* Kumar and Clark’s Clinical Medicine, 9th Edition; Long Cases in Clinical Medicine, ABM Abdullah Page: 61

How to make a diagnosis of asthma

Compatible clinical history plus either/or :

• FEV1 ≥ 15%¹ (and 200 mL) increase following administration of a bronchodilator/trial of corticosteroids
• > 20% diurnal variation on ≥ 3 days in a week for 2 weeks on PEF diary
• FEV1 ≥ 15% decrease after 6 mins of exercise

¹Global Initiative for Asthma (GINA) definition accepts an increase of 12%.

* Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 668

Acute exacerbation of COPD (Chronic obstructive pulmanary disease).

Patient is young adult, lifelong nonsmoker with positive family history of asthma, seasonal variation and morning dipping – all are againt the diagnosis of COPD.

* Short and Long Cases in Clinical Medicine, HN Sarker Page: 230

In chronic bronchitis, there is presence of cough with sputum production not attributable to other causes, on most of the days for at least 3 consecutive months in a year for at least 2 successive years.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 61

Cardiac asthma means left ventricular failure in which

• the patient usually presents with sudden severe dyspnea and cough with profuse mucoid expectoration.
• On examination, there are bilateral basal crepitations and no rhonchi or wheeze.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 61

* Long Cases in Clinical Medicine, ABM Abdullah Page: 64

* Long Cases in Clinical Medicine, ABM Abdullah Page: 69

We can manage acute severe asthma by the followings—

• Urgent hospitalization and send blood for ABG.
• Nebulized salbutamol
  • Adult: 5 mg 2–4 hourly
  • Children: 0.15–0.3 mg/kg/dose every 20 minutes for 3 times or continuously.
• Propped up position/ head up position
• Oxygen
  • High-flow/60%.
  • In children, 4–6 L/min (40–60%) through oxygen hood/ head box
• Prednisolone 40 mg orally (or hydrocortisone 200 mg IV if patient cannot swallow or vomit).
  • Child dose:
    • Inj. hydrocortisone 3–4 mg/kg/dose 4–6 hourly or,
    • Prednisolone 2 mg/kg/day for 3–5 days or as necessary.
• IV access, chest X-ray, send blood for urea and electrolytes, theophylline level.
• If condition does not improve, nebulized ipratropium bromide may be added
  • Administer repeat salbutamol 5mg + ipratropium bromide 0.5 mg nebulizer.
  • If failure to respond, continuous salbutamol nebulizer 5–10 mg/hr.
• If not respond, consider
  • IV magnesium sulfate 1.2–2 gm over 20 mins, or
  • Aminophylline 5 mg/kg loading dose over 20 mins followed by a continuous infusion at 1 mg/kg/hr.
• Correct fluid and electrolytes (esp. K⁺ ) (repeated use of salbutamol may cause hypokalemia).
• In refractory cases
  • Mechanical ventilation and for children, PICU support.

Figure: Immediate treatment of patients with acute severe asthma.

Note:

Arterial blood gases are measured. If PaCO₂ > 7 kPa, ventilation should be considered.

* Pre-exam preparation for medicine, HN Sarker; Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 97; Long Cases in Clinical Medicine, ABM Abdullah Page: 65; Figure: Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 672; 

Nebulized salbutamol.

* Pre-exam preparation for medicine, HN Sarker

As follows:

• Repeated PEFR in every 15 to 30 min
• Pulse oxymetry (SaO₂ should be kept > 92%)
• Repeat arterial blood gas analysis
• X-ray chest to exclude pneumothorax.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 65

Note

• Sedative is contraindicated in acute severe asthma
• No role of chest physiotherapy, antihistamine, antitussive drugs in acute attack.

* Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 672; Long Cases in Clinical Medicine, ABM Abdullah Page: 65

As follows:

• Stable on discharge medication
• Without nebulisation for at least 24 hours
• PEFR 75% of predicted or personal best.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 66

Management of chronic asthma is stepwise to achieve optimum control.

General measures

• Patient education about disease process, compliance, inhaler technique, peak flow monitoring, and self management.
• Avoidance of known precipitants.
• Smoking cessation.
• Immunizations against influenza and pneumococcus.

Drug therapy

1. Step 1
   • Occasional use of inhaled short-acting β2- adrenoreceptor agonist bronchodilators: salbutamol or terbutaline.
2. Step 2
   • Inhaled β2-agonists as required (Step 1)+
   • Low dose inhaled corticosteroids (ICS) such as beclomethasone (200–800 μgm/day), budesonide or leukotriene modifier.
3. Step 3
   • Inhaled β2-agonists as required (Step 1)+
   • Medium or high dose ICS Or,
     • Low dose ICS +
       • long-acting β2-agonists Or,
       • leukotriene modifier. Or,
       • sustained release theophylline.
4. Step 4
   • Inhaled β2-agonists as required (Step 1)+
   • Medium or high dose ICS +
   • Long-acting β2-agonists +/–
     • Leukotriene modifier +/–
     • Sustained release theophylline
5. Step 5
   • Step 4 +
   • Oral steroid +/–
     • Anti-IgE treatment.

Step care management in children, age <5 years:

Step care management in children, age 6-12 years:

Figure: Stepwise approach to asthma therapy according to the severity of asthma and ability to control symptoms.

* Short and Long Cases in Clinical Medicine, HN Sarker Page: 231; Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 98, 99; Figure: Harrison’s Principles of Internal Medicine, 19th Edition Page: 1679

If patient’s asthma is under control, then at every 3 months interval, reduce the dose of inhaled corticosteroids by 25 to 50%.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 66

As follows:

• Methotrexate
• Cyclosporine
• Intravenous immunoglobulin
• Etanercept
• Anti-IgE monoclonal antibody (omalizumab).

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

As follows:

• Omalizumab, a monoclonal antibody directed against IgE, can be given subcutaneously 2 to 4 weekly
• Bronchoplasty – a stent is applied to dilate constricted bronchi
• Bronchothermoplasty – hyperplastic bronchial smooth muscle is reduced by thermal coagulation.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

If the patient develops severe asthma or loss of control at any step during therapy, a short course of oral corticosteroid is given. This is called rescue therapy.

Tablet prednisolone 30 to 60 mg daily (1 to 2 mg/kg daily for children) is given in a single morning dose or two divided doses for 3 to 14 days. Tapering is not necessary, if it is not given for more than 3 weeks.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

Indications are:

• Morning symptoms persist till mid-day
• Onset or worsening of sleep disturbance by asthma
• Progressively diminishing response to inhaled bronchodilators
• Symptoms severe enough to require treatment with nebulized or injected bronchodilators
• Symptoms and PEF get progressively worse day by day
• PEFR falls below 60% of patient’s personal best recording.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

When it is given for more than 3 weeks.

* Pre-exam preparation for medicine, HN Sarker

The patient should follow the rule of 5:

• The patient should be sitting comfortably in up right position.
• Give 5 puffs of bronchodilator inhaler with a large volume spacer.
  • Initially 5 puffs (1 puff and 5 sucks) at 5 minutes interval through spacer up to 5 times (25 puffs) within 1 hour.
  • If no improvement, the patient should go to the nearby hospital.
• If spacer is not available, the patient should take the puffs in the above rule but hold breath for 5 seconds for each puff.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

Figure: How to use a metered-dose inhaler

* Davidson’s Principles and Practice of Medicine, 22nd Edition Page: 670

It is a type of asthma in which there is chronic dry cough with or without sputum eosinophilia, but no abnormalities in airway function. It is also called eosinophilic bronchitis, common in young children. Cough is the only symptom, mostly at night. Examination during day may not reveal any abnormality. Cough may be increased with exercise, exposure to dust, strong fragrances or cold air. Methacholine challenge test is positive.

Clinical criteria for diagnosis:

• Dry cough persisting more than 6 to 8 weeks
• Presence of bronchial hyper-responsiveness
• Absence of dyspnea and wheeze.

Treatment : Should be according to the stepwise approach for long-term. Nedocromil sodium is effective. Also consider the following points:

• Allergic rhinitis should be treated, if present.
• Gastroesophageal reflux disease should be treated with proton pump inhibitor (e.g. omeprazole) and/or gastric prokinetic agent (e.g. domperidone).
• Any environmental factors like cold, dust, fume, etc. should be avoided.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 62

When exercise produces asthma, it is known as exercise-induced asthma. 10% or more reduction of FEV1 after exercise is diagnostic.

Cold dry air that enters into the lungs during exercise is the main trigger factor. Increased ventilation results in water loss from the pericellular lining fluid of the respiratory mucosa trigger mediator release. Heat loss from the respiratory mucosa is also involved.

Treatment:

• Single dose short acting β2 agonist, sodium chromoglycate or nedocromil sodium immediately before exercise should be used.
• Inhaled corticosteroid twice daily for 8 to 12 weeks reduces severity.
• If abnormal spirometry and persistent symptoms- inhaled corticosteroid with long acting β2
• Leukotriene receptor antagonist may be used.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 63

It may be defined as “asthma induced at work by exposure to occupation related agents, which are mainly inhaled at the workplace”. The most characteristic feature is symptoms that worsen on work days and improves on holidays.

Atopic individual and smoker are at increased risk. Commonly found in chemical workers, farmers, grain handlers, cigarette manufacturers, fabric, dye, press and printing workers, laboratory workers, poultry breeders, wood and bakery workers.

Measurement of 2 hourly peak at and away from work is helpful for diagnosis.

Treatment:

• Avoidance of further exposure
• Using mask at work
• If no response, step care asthma management plan.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 63

Symptoms of asthma that occurs after use of certain drugs such as aspirin, beta blocker, some nonsteroidal anti-inframmatory drugs (NSAIDs), etc. These drugs can cause bronchospasm.

Treatment:

Avoidance of triggering drugs. Safe NSAIDs are paracetamol, tramadol, also etoricoxib.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 63

Some patients with asthma have more troublesome disease reflected by:

• High medication requirements to maintain disease control or
• Persistent symptoms, asthma exacerbation, or airflow obstruction despite high medication use.
• This group is called refractory asthma.

Treatment:

• Home nebulization—continuous or as required
• Vaccination—influenza, measles, pneumococcal vaccine
• Anti-IgE (omalizumab), sublingual immunotherapy
• Disease modifying agent—methotrexate, cyclosporine, gold salt
• Patient’s education
• Identifying pitfalls of management.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 67

This is an unusual variant of asthma characterized by severe, life-threatening attacks that may occur within hours or even minutes without little or no warning symptoms. Patients are at risk of sudden death although their asthma may be well controlled in between attacks.

Management:

• The patient should be advised to keep emergency supplies of medications at home, in the car and at work.
• There should be oxygen and resuscitation equipments at home and at work.
• Nebulized b2 agonists should be available at home and at work. Inhaled long acting b2 agonists with a corticosteroid can be very effective.
• Self injectable epinephrine should be kept at home, at work and should be carried by the patent at all times.
• Prednisolone 60 mg.
• Medic Alert bracelet.

On developing wheeze, patient should attend the nearest hospital immediately. Direct admission to ICU may be required.

* Long Cases in Clinical Medicine, ABM Abdullah Page: 68