Asthma

By: Courtney DeNicola

What is Asthma?

– Asthma is a complex syndrome where chronic inflammation in the lower airways results in variable airflow obstruction and bronchial hyper-responsiveness.

– Asthma usually presents in recurrent episodes of coughing, wheezing, breathlessness, and chest tightness.

Prevalence

– Asthma affects as many as 300 million people worldwide

– This number is expected to increase to 400 million by 2025

– Asthma accounts for 1 in every 250 deaths worldwide

– Asthma results in 250,000 deaths each year worldwide

Pathophysiology of Asthma

– Asthmatic airways can exhibit lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, and mucus gland hypersection.

– This contributes to the physical symptoms a patient may exhibit during an episode

– Eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus are greater in number in an asthmatic.

– Allergies play a large role in asthma because certain triggers may cause an asthma “attack”

Pathophysiology of Asthma- Immune Response– IgE antibodies in the lungs respond to a foreign object, the allergen/trigger in this

case.

– The IgE antibodies attach to the Mast cells, which contain and release histamine.

– The histamine causes a reaction in the lungs; however, this reaction is usually too strong and causes the symptoms of asthma.

– When an allergen triggers the immune response, the smooth muscles of the airways spasm and thicken, and excess mucous is secreted into the airway.

– Combined, both reactions decrease the opening of the lumen so less air can flow.

Symptoms

– Classic symptoms include:

– Coughing, usually that is worse at night or early in the morning

– Wheezing

– Chest tightness

– Shortness of breath

Impact on Life

– Asthma has no major impact on life expectancy. If the individual takes care of themselves properly they should have no major issues.

– Long term use of inhaled corticosteroids can impact the growth of children. If the child is monitored and given the proper dosage they should meet their growth percentiles.

– Delayed onset of puberty by 1-2 years is fairly common in children with asthma

– Asthma is typically a life long illness. It can be well controlled with medications and symptoms may only present when the individual is triggered by an allergen.

Risk Factors

– There are many risk factors linked to asthma. Some include:

– Race/ethnicity

– Tobacco smoke exposure

– Farm animal exposure

– Family size and birth order

– Occupational exposure

– Diet and nutrition

– Viral respiratory infections

Genetics

– Asthma has significant genetic influences, as well as environmental factors and triggers

– Heritability estimates vary between 35%-95%

– It is not completely understood how asthma is passed genetically- however, it is believed that it is caused by multiple interacting genes that either have a protective effect or contribute to the disease pathogenesis

– Each gene can also be influenced by the environment

Inheritance

– It is believed that asthma is caused by multiple interacting genes influenced by the environment, but most studies point to the acquirement of asthma by inheritance

– The earliest studies suggested an autosomal dominant inheritance, while preliminary pedigree analysis showed autosomal recessive pattern. Studies have shown mutations in several genes.

– Due to the complexity, there are many ways asthma could be inherited.

– Asthma is familial with a non-Mendelian pattern of inheritance and polymorphisms in over 100 genes.

Links to Asthma

– Chromosomes 5, 6, 11, 12, and 14 have all been linked to asthma

– 5 is the most promising site

– Through positional cloning, 5 genes and gene complexes have been identified as links to asthma:

– ADAM33

– PHF11

– DPP10

– GRPA

– SPINK5

Candidate Gene Association Studies– Straightforward study where the researcher searches for an enrichment of a

marker, insertion/deletion allele, or haplotype (combination of alleles) in cases compared to controls.

– Genes studied were selected based on their known function and likeliness to be involved in pathogenesis

– Essentially the researcher looks for something different in those with asthma compared to those without.

– Many genetic studies of asthma have used this type of study and have been successful.

Linkage Studies

– Used in families with at least two affected relatives (usually siblings)

– The researcher looks for alleles at marker loci that are shared by both siblings more than 50% of the time

– Linkage evidence is reported as a likelihood ration (log of odds in favor of linkage)

– Most scores represent greater than 1000 to 1 odds in favor of linkage.

Genome-wide Association Studies– This type of study can detect risk variants without studying families

– The study uses the candidate gene approach to include markers that “tag” all common variation in the genome

Other Studies

– A study in Europe using segregation analysis showed evidence of a two-allele gene with codominant inheritance (assuming a major gene was involved in pathogenesis)

– One study among nuclear families showed evidence of a polygenic or oligogenic model with some evidence of a recessive gene (only explains part of the segregation)

– Another study showed that total serum IgE concentration levels are highly inheritable and have a strong association between atopy and bronchial hyper-responsiveness- may be involved in the pathogenesis of asthma.

Epigenomics

– Asthma has been shown to have epigenetic mechanisms from air pollution and tobacco smoke.

– Cases of prenatal exposure to cigarette smoke and traffic-related air pollution have shown to influence development of asthma

– Cleaning agents, viruses, exposure to endotoxin, and certain vaccinations have all shown to influence the development and progression of asthma.

– High fruit, vegetable, and oily fish consumption by the mother have shown lower risks of asthma in offspring.

Genetic Testing to Diagnose

– Since there are so many genes that could be linked to asthma, there is no definitive test that can predict if a baby or child will have asthma. There is no test to predict or diagnose asthma at this time.

– If a test was created and shown to be valid and reliable, the ethical concerns are minimal. Asthma is not a life-altering disease and can be treated with ease most of the time. It may be beneficial for parents to know if their child will develop asthma so they can be alert for symptoms.

Current Research

– Current genetic research has been focused on intermediate phenotypes that can be measured objectively.

– The phenotypes include bronchial hyper-responsiveness, lung function, serum IgE, allergen skin test response, and blood eosinophil count.

– Researchers believe that the studies of intermediate phenotypes may lead to the discovery of susceptibility genes for asthma or allergic diseases

– Researchers are also investigating links to specific genes that influence asthma

Case Study

– 9 year old Sophia is brought to the emergency room by her parents. Sophia is exhibiting audible wheezing, a tight, dry cough ,and dusky mucous membranes. She grabs her chest and says “I’m having trouble breathing.”

Case Study

– You first assess Sophia. Her vital signs are: 115/75, HR 146, RR 32, O2 87%, temp 98.7F. You can hear decreased lung sounds with faint expiratory wheezing.

– Her parents inform you that she has asthma, and uses a rescue inhaler as needed, but they couldn’t find her inhaler. They report that she was playing at a park with her friends when the incident occurred.

– What nursing diagnosis can be applied to this case?

Case Study

– Ineffective airway clearance related to bronchoconstriction as evidenced by wheezing, increased respirations, and chest tightness.

– Ineffective breathing pattern related to bronchospasm as evidenced by wheezing, dusky mucous membranes, tachycardia, and tachypnea.

– What should you do next?

Case Study

– Sophia seems to be having a moderate exacerbation. You administer a nebulizer treatment and supplemental oxygen and her condition begins to improve. The doctor writes an order for a corticosteroid. You are able to hear increased wheezing and breath sounds, and her vital signs improve. Sophia is admitted to the hospital to be monitored.

Case Study

– What kind of information can Sophia benefit from?

– What kind of information can Sophia’s parents benefit from?

Case Study

– Sophia could benefit from education at her reading/comprehension level. Diagrams and pictures may illustrate what happened during her exacerbation of asthma. It could be useful to explain how and when to use her inhaler, and when to tell her parents something is wrong.

– Sophia and her parents may benefit from joining a support group for asthma. In our area, there is a support group called “Parents Having Allergic Children Team” that meets at Paoli hospital. They may have been uneducated on the fact that they need to keep a rescue inhaler available at all times. You may want to investigate why they didn’t have the inhaler available, and if she has one at school.

Resources

– Gibbons, G. (2013). What Are the Signs and Symptoms of Asthma?” National Heart, Lung, and Blood Institute.

– Ober, C., & Yao, T.-C. (2011). The Genetics of Asthma and Allergic Disease: A 21st Century Perspective. Immunological Reviews, 242(1), 10–30. National Center for Biotechnology Information. Genes and Disease. 1998.

– Fireman, P. (2003). Understanding asthma pathophysiology. Allergy Asthma Proc. 24(2):79-83

– Ober, C., & Yao, T.-C. (2011). The Genetics of Asthma and Allergic Disease: A 21st Century Perspective. Immunological Reviews, 242(1), 10–30. http://doi.org/10.1111/j.1600-065X.2011.01029.x