Respiratory disease

Asthma affects 300 million people worldwide and is characterized by respiratory symptoms that burden patients and can lead to exacerbations which require medical attention and can be fatal. Common symptoms of asthma include wheezing, chest tightness, cough and shortness of breath. These symptoms are caused by inflammation and hyperreactivity in the airways leading to bronchoconstriction or airway narrowing. There are many triggers for patients with asthma including dust and allergens, pollution, cigarette smoke and even exercise or stress. Identifying and avoiding these triggers is the first step towards managing asthma.

Asthma cannot be cured but it can be controlled with a variety of medications in addition to avoiding common triggers. Asthma medications can be: A.relievers (“rescue” medications helping quickly in an asthma attack) or B. controllers (preventing asthma attacks). Relievers are bronchodilators with rapid onset of action. Every patient with asthma should be given a short acting or “rescue” inhaler to help with sudden-onset symptoms. The most common type of rescue inhaler is albuterol(INN salbutamol) which is a short acting beta-2 agonist (SABA). Albuterol selectively stimulates beta-2 adrenoceptors which leads to relaxation of smooth muscle in the lungs, and opens up the airways to relieve the symptoms of asthma. The peak effects of albuterol occur within 30 minutes which is ideal for managing symptoms when they occur. Other SABAs include levoalbuterol, the R-isomer of albuterol, fenoterol and terbutaline. Short-acting muscarinic antagonists (SAMA, e.g. ipratropium) and xanthines (aminophylline – only i.v.) can be also used to dilate the bronchi and relieve acute asthma attacks.

In addition to a rescue inhaler, most patients with persistent asthma symptoms should use a “controller” medication as well. Persistent asthma is defined as having symptoms requiring the use of a rescue inhaler more than two times per week. Control inhalers are categorized by their mechanism and include inhaled corticosteroids, long-acting beta-2 agonists (LABA), and long-acting muscarinic antagonists (LAMA). Inhaled corticosteroids work to decrease the inflammation in the lungs thus targeting the source of the disease, making these agents the preferred choice. Long-acting beta-2 agonists such as salmeterol can be added to inhaled corticosteroids in patients who are not controlled on their current treatment but should never be used as monotherapy. Long-acting beta-2 agonists work the same way as albuterol, but they have a longer duration of action making them ideal for preventing symptoms. Their slower onset of action, however, precludes their use for treatment of acute symptoms. Long-acting anticholinergic agents like tiotropium, are not considered first-line but can be used in patients who don’t respond to or still have symptoms while on inhaled corticosteroids and long-acting beta agonists. Mast cell stabilizers such as cromolyn and nedocromil that are used mostly in allergic conjunctivitis and rhinitis may also have some benefit in asthma. Common agents in each drug class are listed below.

Inhaled Corticosteroids:

Beclomethasone

Budesonide

Ciclesonide

Fluticasone

Mometasone

Long-acting beta-2 agonists (LABAs) approved to treat asthma:

Salmeterol

Formoterol

Long acting anticholinergics approved to treat asthma:

Tiotropium

Mast cell stabilizers:

Cromolyn

Nedocromil

Some patients may require systemic medications to control their asthma symptoms. Retard formulations of xanthines (oral theophylline) can be used for this purpose. Leukotriene inhibitors (leukotriene receptor antagonists such as montelukast and inhibitors of leukotriene synthesis such as zileuton) work by reducing airway inflammation, edema and smooth muscle contraction. These agents are given orally and are often used to treat allergies in addition to asthma. Monoclonal antibodies against IgE (omalizumab) and against IL-5 (reslizumab, mepolizumab, benralizumab) can be injected s.c. or i.v. every 2-4 weeks in allergic/eosinophilic asthma. These drugs will not help acute symptoms, but can be used to prevent symptoms in the future. For patients that are experiencing an acute asthma exacerbation, systemic steroids should be used to decrease inflammation. Patients with an increased heart or respiratory rate with low oxygen saturations (<90%) should be admitted to the hospital for treatment with a short-acting beta-2 agonist, systemic steroids and oxygen therapy.

Molly Graveno, Kelly Karpa

COPD is a largely preventable lung condition. The main risk factor for development and exacerbation of COPD is tobacco smoking, but environmental and/or occupational exposure to pollutants is also implicated in the pathology of COPD. A very small number of cases are caused by genetic defects or impaired lung development. Smoking cessation is the most effective way to prevent COPD, or to reduce symptoms and exacerbations from established disease.

The lung damage in COPD is progressive and becomes incurable, with persistent airflow limitation and other respiratory complications (infections, wheeze, chronic cough, sputum production) being the most prevalent symptoms. Small airways disease (obstructive bronchiolitis), parenchymal destruction (emphysema), and fibrotic processes underlie the chronic tissue damage and airflow limitation in COPD.

The aims of COPD management and treatments are to reduce symptoms, exacerbations and improve patients’ quality of life.

Management of stable COPD:

Inhalation short-acting bronchodilators are the initial therapeutic option, to relieve breathlessness and exercise limitation. They can be in the form of a short-acting beta₂ receptor agonist (SABA; salbutamol) or a short-acting muscarinic receptor antagonist (SAMA; ipratropium).

Step-up treatment options, for patients who continue to be breathless or have exacerbations, include long-acting beta₂ agonists (LABA; salmeterol and formoterol) and long-acting muscarinic antagonist (LAMA; tiotropium; in place of the SAMA). Use of SABAs can continue as required.

Inhaled corticosteroid (ICS) agents (budesonide, beclometasone, fluticasone) can be tried, if the bronchodilator drugs alone are failing to prevent moderate-severe exacerbations, and symptoms are adversely impacting quality of life. A large range of combination formoterol (LABA)/ICS medications is available.

Prophylactic use of antibacterials (e.g., azithromycin) can be considered in cases where other lung pathologies, QT prolongation, sputum culture and sensitivity testing have been carried out to justify antibacterial use.

Respiratory specialists can initiate treatment with roflumilast (a phosphodiesterase-4 inhibitor) as an add-on option for patients with severe COPD with chronic bronchitis.

Mucolytic treatment for productive cough (carbocysteine, acetylcysteine), and antitussives should be used when appropriate.

Management of COPD exacerbations:

Higher dose short-acting inhaled bronchodilators can be administered through a nebuliser or hand-held device to reduce breathlessness.

A short course of prednisolone can be considered for hospitalised patients (in the absence of contraindications). If oral corticosteroids are considered as an appropriate option, the dose and length of treatment depend on the severity of the exacerbation. Potential adverse effects of systemic glucocorticoids that may require mitigation, include hyperglycemia (in patients with diabetes mellitus), fluid retention, hypertension, and pneumonia.