RT Book, Section
A1 Weiss, Scott
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102704578
T1 Asthma
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102704578
RD 2024/04/19
AB Disease  summary:Asthma  is  a  disease  that  is  defined  by  reversible  airflow  obstruction,  airway  inflammation,  and  respiratory  symptoms  of  wheezing  and  cough.  The  disorder  is  closely  associated  with  allergy,  or  immediate  type  hypersensitivity  to  aeroallergens.  Roughly  70%  of  all  childhood  asthmatics  are  allergic.  Epidemiologically  the  disease  is  very  common,  affecting  roughly  6%  of  the  US  population.  Asthma  commonly  starts  in  early  childhood.  It  has  a  variable  early  natural  history;  roughly  30%  of  children  have  wheezing  with  colds  or  occasionally  apart  from  colds  in  the  first  year  of  life.  This  decreases  to  about  15%  at  age  3,  with  a  similar  percentage  at  age  6.  Unfortunately,  the  phenotype  does  not  breed  true,  and  clinicians  cannot  predict  which  of  those  children  wheezing  at  age  1  will  be  wheezing  at  age  3  or  age  6.  Adult  asthma  is  often  a  recrudescence  of  childhood  disease  and  has  a  less  clear-cut  relationship  to  allergy.  There  is  a  growing  body  of  evidence  that  persistent  asthma  leads  to  reduced  growth  in  lung  function  and  an  increased  risk  for  the  development  of  chronic  obstructive  lung  disease  (COLD)  in  adult  life.  Major  morbidity  is  incurred  from  uncontrolled  disease  by  reduced  quality  of  life,  days  lost  from  work,  hospitalizations,  and  emergency  room  visits.  More  details  of  the  clinical  features  of  asthma  are  given  in  references  1  and  2.,Differential  diagnosis:In  children  asthma  can  be  confused  with  chronic  bronchitis,  cystic  fibrosis,  bronchopulmonary  dysplasia,  and  bronchiectasis.  Asthma  in  adults  is  often  confused  with  COLD.  It  can  be  differentiated  from  chronic  obstructive  pulmonary  disease  (COPD)  via  chest  x-ray,  and  spirometry  (lung  function  tests)  before  and  after  a  short-acting  bronchodilator.  Occasionally  a  computed  tomography  (CT)  scan  is  helpful  in  distinguishing  these  two  conditions.  In  children,  asthma  must  be  differentiated  from  bronchiolitis  or  bronchitis.  This  is  usually  done  by  the  same  sort  of  clinical  testing,  for  example,  x-ray  and  spirometry,  and  clinical  response  to  anti-inflammatory  medication.Monogenic  forms:None  describedFamily  history:Roughly  two-thirds  of  all  asthma  patients  will  have  a  family  history  of  allergies  or  asthma  in  a  first-degree  relative.  This  does  not  prove  a  genetic  origin  to  the  disease  as  this  also  occurs  with  any  prevalent  complex  condition  of  reasonably  high  prevalence.Twin  studies:Concordance  for  dizygotic  twins  ranges  from  15%  to  40%  and  for  monozygotic  twins  ranges  from  50%  to  80%.Environmental  factors:The  most  important  environmental  risk  factors  are  aeroallergens  (house  dust  mite,  alternaria,  cockroach)  and  smoking.  In  utero  and  postnatal  passive  smoking  are  important  risk  factors  in  children  increasing  the  disease  occurrence  from  40%-200%.  Active  smoking  is  important  in  adolescents  and  adults.  Additional  environmental  exposures  of  importance  are  viral  infections  and  pets,  particularly  cats  and  dogs.  In  adults,  postmenopausal  estrogen  is  a  risk  factor.Genome-wide  associations:This  analytic  approach  that  uses  single-nucleotide  polymorphisms  (SNPs)  across  the  whole  genome  has  identified  a  three-gene  locus  on  chromosome  17q21  containing  ORMDL3,  GSDMB,  and  ZPBP2  as  the  strongest  locus  for  asthma.  Other  genes  identified  by  this  approach  include  IL1RL1/IL18,  TSLP,  HLADQ,  IL2RB,  SLC22A5,  RORA,  IL33,  and  SMAD3.Pharmacogenomics:Genome-wide  association  studies  (GWASs)  have  implicated  the  GLCCI1  and  the  T  gene  as  determinants  of  change  in  lung  function  with  inhaled  corticosteroid.  Short-acting  ...