Acute severe asthma

Cause

The cause for acute severe asthma attacks is still unknown and experts are also unsure of why it developed and why it does not respond to typical asthma treatments.

• Not seeing a doctor regularly, therefore asthma is not under good control
• Coming in contact with asthma triggers
• Allergies or severe allergic reactions
• Not using the peak flow meter and not taking asthma medication as directed by a primary care physician (PCP) correctly
• Not following an asthma action plan correctly
• Respiratory infections
• Severe stress
• Cold weather
• Air pollution
• Exposure to chemicals and other irritants
• Smoking

Mechanism

Inflammation in asthma is characterized by an influx of eosinophils during the early-phase reaction and a mixed cellular infiltrate composed of eosinophils, mast cells, lymphocytes, and neutrophils during the late-phase (or chronic) reaction. The simple explanation for allergic inflammation in asthma begins with the development of a predominantly helper T2 lymphocyte–driven, as opposed to helper T1 lymphocyte–driven, immune milieu, perhaps caused by certain types of immune stimulation early in life. This is followed by allergen exposure in a genetically susceptible individual.

Specific allergen exposure (e.g., dust mites) under the influence of helper T_h2 helper T cells leads to B-lymphocyte elaboration of immunoglobulin E (IgE) antibodies specific to that allergen. The IgE antibody attaches to surface receptors on the airway mucosal mast cells. One important question is whether atopic individuals with asthma, in contrast to atopic persons without asthma, have a defect in mucosal integrity that makes them susceptible to penetration of allergens into the mucosa.

Subsequent specific allergen exposure leads to cross-bridging of IgE molecules and activation of mast cells, with elaboration and release of a vast array of mediators. These mediators include histamine; leukotrienes C4, D4, and E4; and a host of cytokines. Together, these mediators cause bronchial smooth muscle constriction, vascular leakage, inflammatory cell recruitment (with further mediator release), and mucous gland secretion. These processes lead to airway obstruction by constriction of the smooth muscles, edema of the airways, influx of inflammatory cells, and formation of intraluminal mucus. In addition, ongoing airway inflammation is thought to cause airway hyperreactivity characteristic of asthma. The more severe the airway obstruction, the more likely ventilation-perfusion mismatching will result in impaired gas exchange and low levels of oxygen in the blood.

Diagnosis

Severe acute asthma can be diagnosed by a primary care physician (PCP). A PCP will ask questions in regards to symptoms and breathing; they will also ask if fatigue or wheezing has been experienced when breathing in or out; and also test using a peak expiratory flow and an oxygen saturation.

Status asthmaticus can be misdiagnosed when wheezing occurs from an acute cause other than asthma. Some of these alternative causes of wheezing are discussed below.

Extrinsic compression

Airways can be compressed from vascular structures, such as vascular rings, lymphadenopathy, or tumors.

Congestive heart failure

Airway edema may cause wheezing in CHF. In addition, vascular compression may compress the airways during systole with cardiac ejection, resulting in a pulsatile wheeze that corresponds to the heart rate. This is sometimes erroneously referred to as cardiac asthma.

Differential diagnoses

• Allergic bronchopulmonary aspergillosis
• Aspiration syndromes
• Bronchiectasis
• Bronchiolitis
• Bronchiolitis obliterans
• Chronic bronchitis
• Chronic obstructive pulmonary disease (COPD)
• Eosinophilic granulomatosis with polyangiitis
• Croup
• Cystic fibrosis
• Emphysema
• Foreign bodies of the airway
• Gastroesophageal reflux disease
• Heart failure
• Idiopathic pulmonary arterial hypertension
• Inhalation injury
• Pulmonary artery sling
• Vocal cord dysfunction

Treatment

Starting with first line treatments like inhalers the acute, short acting beta agonists and oxygen therapy then advance treatment include interventions like intravenous (IV) medications (e.g. magnesium sulfate), aerosolized medications to dilate the airways (bronchodilation) (e.g., albuterol or ipratropium bromide/salbutamol), and positive-pressure therapy, including mechanical ventilation. Multiple therapies may be used simultaneously to rapidly reverse the effects of status asthmaticus and reduce permanent damage of the airways. Intravenous corticosteroids and methylxanthines are often given. If the person with a severe asthma exacerbation is on a mechanical ventilator, certain sedating medications such as ketamine or propofol, have bronchodilating properties. According to a new randomized control trial ketamine and aminophylline are also effective in children with acute asthma who responds poorly to standard therapy.

Recent research

A recent study proposed that the interaction between host airway epithelial cells and respiratory viruses is another aspect of innate immunity that is also a critical determination of asthma. It was also proposed that a rationale for how antiviral performance at the epithelial cell level might be improved to prevent acute infectious illness and chronic inflammatory disease caused by respiratory viruses.

Another study aimed to show that experimental asthma after viral infection inmate depended on Type I IFN-driven up-regulation of the high-affinity receptor for IgE (FcεRI) on conventional dendritic cells (cDCs) in the lungs. The study found that a Novell PMN-cDc interaction in the lung is necessary for a viral infection to induce atopic disease.

Epidemiology

Status asthmaticus is slightly more common in males and is more common among people of African and Hispanic origin. The gene locus glutathione dependent S-nitrosoglutathione (GSNOR) has been suggested as one possible correlation to development of status asthmaticus.