Airway remodelling, or airway remodeling, is a potential complication of certain endotypes (subtypes) of asthma. It is the sum of changes that occur in the airways of some asthmatic people compared to people without the disease. [1] [2]
Asthma is characterised, in part, by recurrent episodes of reversible airway obstruction; however, in some patients, a degree of irreversible airway obstruction develops over time, leading to lung function decline and fibrosis. Existing airway remodelling may also contribute to bronchoconstriction in acute asthma exacerbations. [1] [2]
Airway remodelling is a multifaceted process involving multiple airway tissues. These include goblet cell hyperplasia, leading to increased mucus production, and airway smooth muscle hypertrophy (or smooth muscle cell hyperplasia), leading to the release of pro-inflammatory and pro-fibrotic messengers contributing to subepithelial fibrosis. [1] [2] Subepithelial fibrosis in airway remodelling is also associated with fibroblast-to-myofibroblast transition mediated by transforming growth factor β. [2]
Airway remodelling is not found at birth, but may be detected as soon as at 2 years of age in some patients. [1]
Airway remodelling had traditionally been considered a consequence of chronic airway inflammation. However, while attenuating chronic airway inflammation using inhaled corticosteroids is effective at preventing asthma exacerbations, it does not seem to impact the progression of airway remodelling. [1] [2] Also, as mentioned, airway remodelling may be seen as soon as at 2 years of age, before any airway inflammation is detectable. [1] Thus, airway remodelling is now considered to occur in conjunction with chronic airway inflammation rather than because of it. [3]
Bronchial thermoplasty is the only treatment modality designed to combat a hallmark of airway remodelling; airway smooth muscle hypertrophy. The effects of bronchial thermoplasty on smooth muscle mass are seen up to at least 12 months post-treatment; however, the procedure does not seem to impact other features of airway remodelling. [4]
Thus far, no pharmacological treatment modality for asthma has been developed nor shown to prevent or attenuate the progression of airway remodelling. [1] [2]
While effective at preventing asthma exacerbations, inhaled corticosteroid or bronchodilator treatment has not been shown to prevent or lessen the development of airway remodelling in longitudinal studies. Inhaled corticosteroids may also partly contribute to airway remodelling by reducing epithelial cell adherence. [1] [2]
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise.
Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest pain. Wheezing and nail clubbing may also occur. Those with the disease often get lung infections.
An inhaler is a medical device used for delivering medicines into the lungs through the work of a person's breathing. This allows medicines to be delivered to and absorbed in the lungs, which provides the ability for targeted medical treatment to this specific region of the body, as well as a reduction in the side effects of oral medications. There are a wide variety of inhalers, and they are commonly used to treat numerous medical conditions with asthma and chronic obstructive pulmonary disease (COPD) being among the most notable.
Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation. β2 adrenergic agonists' effects on smooth muscle cause dilation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. They are primarily used to treat asthma and other pulmonary disorders. Bronchodilators are considered an important treatment regime for Chronic obstructive pulmonary disease (COPD) and are usually used in combination with short acting medications and long acting medications in a combined inhaler.
Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath.
Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris, aspiration, herbicides or fluorocarbons and some systemic diseases. If unresolved, continued inflammation can result in irreparable damage such as pulmonary fibrosis.
Long-acting β adrenoceptor agonists are usually prescribed for moderate-to-severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2 agonists such as salbutamol (albuterol), as they have a duration of action of approximately 12 hours in comparison with the 4-to-6-hour duration of salbutamol, making them candidates for sparing high doses of corticosteroids or treating nocturnal asthma and providing symptomatic improvement in patients with COPD. With the exception of formoterol, long-acting β2 agonists are not recommended for the treatment of acute asthma exacerbations because of their slower onset of action compared to salbutamol. Their long duration of action is due to the addition of a long, lipophilic side-chain that binds to an exosite on adrenergic receptors. This allows the active portion of the molecule to continuously bind and unbind at β2 receptors in the smooth muscle in the lungs.
Acute severe asthma, also known as status asthmaticus, is an acute exacerbation of asthma that does not respond to standard treatments of bronchodilators (inhalers) and corticosteroids. Asthma is caused by multiple genes, some having protective effect, with each gene having its own tendency to be influenced by the environment although a genetic link leading to acute severe asthma is still unknown. Symptoms include chest tightness, rapidly progressive dyspnea, dry cough, use of accessory respiratory muscles, fast and/or labored breathing, and extreme wheezing. It is a life-threatening episode of airway obstruction and is considered a medical emergency. Complications include cardiac and/or respiratory arrest. The increasing prevalence of atopy and asthma remains unexplained but may be due to infection with respiratory viruses.
Interleukin 13 (IL-13) is a protein that in humans is encoded by the IL13 gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31.1 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The secondary structural features of IL-13 are similar to that of Interleukin 4 (IL-4); however it only has 25% sequence identity to IL-4 and is capable of IL-4 independent signaling. IL-13 is a cytokine secreted by T helper type 2 (Th2) cells, CD4 cells, natural killer T cell, mast cells, basophils, eosinophils and nuocytes. Interleukin-13 is a central regulator in IgE synthesis, goblet cell hyperplasia, mucus hypersecretion, airway hyperresponsiveness, fibrosis and chitinase up-regulation. It is a mediator of allergic inflammation and different diseases including asthma.
Levosalbutamol, also known as levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Evidence is inconclusive regarding the efficacy of levosalbutamol versus salbutamol or salbutamol-levosalbutamol combinations, though levosalbutamol is believed to have a better safety profile due to its more selective binding to β2 receptors versus β1.
Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system to the fungus Aspergillus. It occurs most often in people with asthma or cystic fibrosis. Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses.
Bronchial thermoplasty is a treatment for severe asthma approved by the FDA in 2010 involving the delivery of controlled, therapeutic radiofrequency energy to the airway wall, thus heating the tissue and reducing the amount of smooth muscle present in the airway wall. This reduces the capacity of the immune system to cause bronchoconstriction through nitric oxide signalling, which is the main root cause of asthma symptoms. Bronchial thermoplasty is normally used to treat patients with severe persistent asthma who do not respond well to typical pharmacotherapy regimens.
Obstructive lung disease is a category of respiratory disease characterized by airway obstruction. Many obstructive diseases of the lung result from narrowing (obstruction) of the smaller bronchi and larger bronchioles, often because of excessive contraction of the smooth muscle itself. It is generally characterized by inflamed and easily collapsible airways, obstruction to airflow, problems exhaling, and frequent medical clinic visits and hospitalizations. Types of obstructive lung disease include; asthma, bronchiectasis, bronchitis and chronic obstructive pulmonary disease (COPD). Although COPD shares similar characteristics with all other obstructive lung diseases, such as the signs of coughing and wheezing, they are distinct conditions in terms of disease onset, frequency of symptoms, and reversibility of airway obstruction. Cystic fibrosis is also sometimes included in obstructive pulmonary disease.
The Firestone Institute for Respiratory Health (FIRH) is a center for the investigation and treatment of respiratory diseases. Based out of St. Joseph's Healthcare in Hamilton, Ontario, Canada, the institute is a clinical facility with strong research directions. FIRH faculty are also heavily involved at McMaster University with education at the undergraduate, graduate, post-graduate and continuing medical education levels.
Eosinophilic bronchitis (EB) is a type of airway inflammation due to excessive mast cell recruitment and activation in the superficial airways as opposed to the smooth muscles of the airways as seen in asthma. It often results in a chronic cough. Lung function tests are usually normal. Inhaled corticosteroids are often an effective treatment.
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms of COPD include shortness of breath and a cough, which may or may not produce mucus. COPD progressively worsens, with everyday activities such as walking or dressing becoming difficult. While COPD is incurable, it is preventable and treatable. The two most common types of COPD are emphysema and chronic bronchitis and have been the two classic COPD phenotypes. However, this basic dogma has been challenged as varying degrees of co-existing emphysema, chronic bronchitis, and potentially significant vascular diseases have all been acknowledged in those with COPD, giving rise to the classification of other phenotypes or subtypes. Emphysema is defined as enlarged airspaces (alveoli) whose walls have broken down resulting in permanent damage to the lung tissue. Chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years. Both of these conditions can exist without airflow limitation when they are not classed as COPD. Emphysema is just one of the structural abnormalities that can limit airflow and can exist without airflow limitation in a significant number of people. Chronic bronchitis does not always result in airflow limitation but in young adults with chronic bronchitis who smoke, the risk of developing COPD is high. Many definitions of COPD in the past included emphysema and chronic bronchitis, but these have never been included in GOLD report definitions. Emphysema and chronic bronchitis remain the predominant phenotypes of COPD but there is often overlap between them and a number of other phenotypes have also been described. COPD and asthma may coexist and converge in some individuals. COPD is associated with low-grade systemic inflammation.
Chronic Mycoplasma pneumonia and Chlamydia pneumonia infections are associated with the onset and exacerbation of asthma. These microbial infections result in chronic lower airway inflammation, impaired mucociliary clearance, an increase in mucous production and eventually asthma. Furthermore, children who experience severe viral respiratory infections early in life have a high possibility of having asthma later in their childhood. These viral respiratory infections are mostly caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV). Although RSV infections increase the risk of asthma in early childhood, the association between asthma and RSV decreases with increasing age. HRV on the other hand is an important cause of bronchiolitis and is strongly associated with asthma development. In children and adults with established asthma, viral upper respiratory tract infections (URIs), especially HRVs infections, can produce acute exacerbations of asthma. Thus, Chlamydia pneumoniae, Mycoplasma pneumoniae and human rhinoviruses are microbes that play a major role in non-atopic asthma.
Asthma triggers are factors or stimuli that provoke the exacerbation of asthma symptoms or increase the degree of airflow disruption, which can lead to an asthma attack. An asthma attack is characterized by an obstruction of the airway, hypersecretion of mucus and bronchoconstriction due to the contraction of smooth muscles around the respiratory tract. Its symptoms include a wide range of manifestations such as breathlessness, coughing, a tight chest and wheezing.
Asthma-Chronic Obstructive Pulmonary Disease (COPD) Overlap (ACO), also known as Asthma-COPD Overlap Syndrome (ACOS) is a chronic inflammatory, obstructive airway disease in which features of both asthma and COPD predominate. Asthma and COPD were once thought of as distinct entities, however in some, there are clinical features of both asthma and COPD with significant overlap in pathophysiology and symptom profile. It is unclear whether ACO is a separate disease entity or a clinical subtype of asthma and COPD. The pathogenesis of ACO is poorly understood, but it is thought to involve both type 2 inflammation as well as type 1 inflammation. The incidence and prevalence of ACO are not well known. The risk factors for ACO are also incompletely understood, but tobacco smoke is known to be a major risk factor.
Asthma phenotyping and endotyping is a novel approach to asthma classification inspired by precision medicine. It seeks to separate the clinical presentations or clusters of signs and symptoms of asthma, known as asthma phenotypes, from their underlying etiologies or causes, known as asthma endotypes.