Asthma: Diagnosis and Management ____________________________________________________________
in 2002. Researchers at Channing Laboratory, Brigham and Women’s Hospital in Boston, were able to link variants of this gene to a familial history of asthma and asthma symptoms. In 2003, two more genes relating to asthma, PHF11 and DPP10, were identified [13; 24]. Results have been mixed regarding the role of Clara cell secretory protein gene variants and the asthma phenotype on the development of asthma, but research seems to indicate a positive, but inconsistent link [25; 26]. . Although causative chromosomal regions and candidate genes are now being revealed, this has not ruled out the influence of environmental factors in asthma development. In 2013, the results of two studies were analyzed to determine the role of genetic and environmental factors, and the researchers found that variants at the 17q21 locus were implicated in the develop- ment of asthma in children with a history of rhinovirus infec- tion with wheezing [27]. This indicates a possible synergistic relationship between genetic and environmental factors in the development of asthma in childhood. These discoveries opened new avenues for research in asthma and allergy, and advances since the early 2010s in genomics technology and epigenetics now offer expanded methods to link genetic variants, providing important information about the molecular mechanisms underlying the complex (epi) genetics of asthma. Genome-wide association studies have highlighted that the majority of identified gene variants are not associated with altered protein function but are instead controlled by non-coding gene regulatory elements. In these studies, (epi)genetic variants were found to be identified in 25.6% of childhood-onset asthma heritability and 10.6% of adult-onset asthma [28], Should a family have a history of allergies and asthma, the first two years of a child’s life are critical; exposure to poten- tial allergens during this time increases the likelihood that a child will develop asthma. In addition, early contacts to such potential allergens may contribute to the severity of the child’s asthma. Genetic tendency toward lung sensitivity may not fol- low a direct line; asthma may bypass a generation or surface in other family branches. The exact mode of inheritance is unclear [8; 15]. PREMATURE BIRTH Premature birth and associated low birth weight have been considered a risk factor for asthma for many years. One study found that school-age children (3 to 17 years of age) who had been very low-birth-weight infants (i.e., less than 1,500 grams or 3.3 pounds) experienced several long-term health, educational, and social effects. This included asthma, which was reported in 20.9% of the children of very low birth weights, 10.7% of children with low birth weight (1,500–2,000 grams), and 8.1% of those who had been of normal weight at birth. However, it was found that very low birth weight was only shown to be a risk factor for asthma among Hispanic and Black children between 6 and 12 years of age, demonstrating racial and age
disparities [29]. The causal link between low birth weight and premature delivery and asthma development has not been completely determined. Poor intrauterine growth and lung and immune system development have long been believed to be the cause; however, additional factors that are often pres- ent in premature infants, including antibiotic use in early life, respiratory syncytial virus (RSV) infection in infancy, vitamin D deficiency, and pneumonia in early childhood, have been associated with the development of asthma and require addi- tional research [29; 30]. Identifying possible risk factors specific to certain patients may allow lifestyle changes or more strenuous observation of symptoms for better control of asthma.
PATHOPHYSIOLOGY
ANATOMY AND PHYSIOLOGY Asthma most prominently affects the respiratory and immune systems, and knowledge of the structures and workings of these systems is vital to an understanding of the condition. The most obviously affected structures of the respiratory system are the bronchial tubes. As the bronchi stretch deeper into the lungs, they subdivide into smaller bronchioles. A pale, thin membrane, known as the bronchial mucosa, lines these bronchial tubes. Mucous glands, which keep airways lubricated with watery mucus, are embedded within the many layers of bronchial lining. Harmful substances stick to the mucus or sputum and are propelled out of the lungs by the movement of the cilia; this mucus production is one way the body fights infection [8; 13]. The outer walls of the bronchial tubes are surrounded by smooth muscles; movement of these muscles controls the size of airway openings, permitting air in or out of the bronchioles. When muscles are relaxed, airways remain open, allowing air to pass through without effort. Upon exhalation, the muscles contract. Contraction can occur with amazing rapidity. When the lungs and/or bronchi are irritated, the muscles contract and narrow the diameter of the tubes. As with all muscle, continued contraction will cause growth or hypertrophy. The muscle itself may become chronically thickened even in its rest- ing state, which narrows the tube further. When a stimulus is encountered, profound narrowing of the bronchial tubes due to muscle constriction, or bronchospasm, can occur within just a few seconds. Such narrowing in its most severe form can result in sudden death from asphyxiation. Usually, automatic reflexes control whether muscles contract or relax [6; 13]. Deep inside the lungs, surrounding each bronchiole, are mil- lions of tiny, balloon-like air sacs called alveoli. These structures provide the environment for the exchange of gases, allowing oxygen from inhaled air to pass into the bloodstream through the capillaries within the sacs [13].
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MDVT1726
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