Respiratory System - Abnormalities

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Human congenital diaphragmatic hernia
Human congenital diaphragmatic hernia[1]

Abnormalities of the respiratory system include not only lung development but also the upper respiratory tract, the supporting musculoskeletal system and the vascular and neural system. In addition, some respiratory problems arise from prematurity of birth or difficulty with the birth process itself.

The functional part of the respiratory system, the alveoli, continue to develop the postnatal period and through childhood (Postnatal alveoli number graph).

Respiratory Links: respiratory | Science Lecture | Lecture Movie | Med Lecture | Stage 13 | Stage 22 | Upper Respiratory Tract | diaphragm | Histology | Postnatal | respiratory abnormalities | Respiratory Quiz | Respiratory terms | Category:Respiratory
Historic Embryology  
1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 1914 Phrenic Nerve | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels | 1934 Right Fetal Lung | 1936 Early Human Lung | 1937 Terminal Air Passages | 1938 Human Histology
International Classification of Diseases - Respiratory
Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | Coelomic Cavity | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | renal abnormalities] | respiratory abnormalities | placenta abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease | ICD-11
Historic Embryology  
1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

  • Maternal asthma is associated with increased risk of perinatal mortality[2] "Asthma is the most common chronic disease during pregnancy and it may have influence on pregnancy outcome. OBJECTIVES: Our goal was to assess the association between maternal asthma and the perinatal risks as well as possible effects of asthma medication. METHODS: The study was based on a nationwide Finnish register-based cohort between the years 1996 and 2012 in the Drug and Pregnancy Database. CONCLUSION: Asthma is associated with increased risks of perinatal mortality, preterm birth, low birth weight, fetal growth restriction (SGA), and asphyxia. Asthma treatment reduces the risk of preterm delivery, but it does not seem to reduce other complications such as perinatal mortality."
  • Longitudinal assessment of lung function in extremely prematurely born children[3] "To assess longitudinally small airway function in children born extremely prematurely and whether there was a correlation between airway function in infancy and at 11-14 years. Thirty-five children with a mean gestational age of 26 weeks had lung function assessed at 1 year corrected and 11-14 years of age. These results demonstrate in those born extremely prematurely there is tracking of airway function during childhood." Birth - Preterm
  • Trends in treatment and in-hospital mortality for neonates with congenital diaphragmatic hernia[4] "We performed a retrospective cohort study in order to examine recent trends in use of post-partum treatments and in-hospital mortality for congenital diaphragmatic hernia (CDH). Survival improved in large subgroups of term or near-term infants with CDH in this 10-year multicenter cohort, temporally associated with increasing use of multiple vasodilators. Use of vasodilators for infants with CDH is increasing despite a lack of evidence supporting efficacy or safety. Prospective research is needed to clarify specific causal effects contributing to improving survival in these infants."
  • Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD).[5] "Surfactant deficiency and the resultant respiratory distress syndrome (RDS) seen in preterm infants is a major cause of respiratory morbidity in this population. Until recently, the contribution of surfactant to respiratory morbidity in infancy was limited to the neonatal period. It is now recognised that inborn errors of surfactant metabolism leading to surfactant dysfunction account for around 10% of childhood interstitial lung disease (chILD)."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Abnormal Respiratory Development'

Takahiro Mitsumura, Yoshiaki Ito, Tomoki Chiba, Takahide Matsushima, Ryota Kurimoto, Yoko Tanaka, Tomomi Kato, Keisuke Uchida, Takashi Ito, Kouhei Yamamoto, Yoshinobu Eishi, Masanobu Kitagawa, Yasunari Miyazaki, Naohiko Inase, Hiroshi Asahara Ablation of miR-146b in mice causes hematopoietic malignancy. Blood Adv: 2018, 2(23);3483-3491 PubMed 30530754

Tetsuji Takabayashi, Yukie Tanaka, Dai Susuki, Kanako Yoshida, Kaori Tomita, Masafumi Sakashita, Yoshimasa Imoto, Yukinori Kato, Norihiko Narita, Tsugihisa Nakayama, Shinichi Haruna, Robert P Schleimer, Shigeharu Fujieda Increased expression of L-plastin in nasal polyp of patients with nonsteroidal anti-inflammatory drug exacerbated respiratory disease. Allergy: 2018; PubMed 30479022

Robert M Burkes, Michael B Drummond Initiating drug therapy in early stage chronic obstructive pulmonary disease: does it impact the course and outcome? Curr Opin Pulm Med: 2018; PubMed 30461533

Sang Jun Lee, Ji Hoon Na, Jinu Han, Young Mock Lee Ophthalmoplegia in Mitochondrial Disease. Yonsei Med. J.: 2018, 59(10);1190-1196 PubMed 30450853

Ryan W Bavis, Alexandra H Millström, Song M Kim, Carolyn A MacDonald, Caitlin A O'Toole, Kendra Asklof, Amy B McDonough Combined effects of intermittent hyperoxia and intermittent hypercapnic hypoxia on respiratory control in neonatal rats. Respir Physiol Neurobiol: 2018; PubMed 30439529

Newborn Respiratory Distress Syndrome

P Thakore, A E Dunbar, E B Lindsay Central diabetes insipidus: A rare complication of IVH in a very low birth weight preterm infant. J Neonatal Perinatal Med: 2018; PubMed 30530977

Laura E Fredenburgh, Mark A Perrella, Diana Barragan-Bradford, Dean R Hess, Elizabeth Peters, Karen E Welty-Wolf, Bryan D Kraft, R Scott Harris, Rie Maurer, Kiichi Nakahira, Clara Oromendia, John D Davies, Angelica Higuera, Kristen T Schiffer, Joshua A Englert, Paul B Dieffenbach, David A Berlin, Susan Lagambina, Mark Bouthot, Andrew I Sullivan, Paul F Nuccio, Mamary T Kone, Mona J Malik, Maria Angelica Pabon Porras, Eli Finkelsztein, Tilo Winkler, Shelley Hurwitz, Charles N Serhan, Claude A Piantadosi, Rebecca M Baron, B Taylor Thompson, Augustine Mk Choi A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS. JCI Insight: 2018, 3(23); PubMed 30518685

G F Yan, X D Cai, C B Zhou, X Y Hong, Y Wang, C M Zhang, Z H Yang, Y C Zhang, Y Cui, Y Q Cui, Y B Cheng, S Y Qian, P F Zhang, Y P Jin, X D Zhu, H Gao, Z P Li, X L Lu, H J Miao, Q Y Zhang, Y M Li, W G Yang, C Y Liu, B Li, Y Li, Z J Bo, J P Chu, X Wang, G P Lu [Multicenter investigation of extracorporeal membrane oxygenation application in pediatric intensive care unit in China]. Zhonghua Er Ke Za Zhi: 2018, 56(12);929-932 PubMed 30518007

Sanja Zivanovic, Alexandra Scrivens, Raffaella Panza, Peter Reynolds, Nicola Laforgia, Kevin N Ives, Charles C Roehr Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants without the Need for Rescue with Nasal Continuous Positive Airway Pressure. Neonatology: 2018, 115(2);175-181 PubMed 30513521

Olufunke Bolaji, Olagoke Erinomo, Olufunmilayo Adebara, Julia Okolugbo, Bartholomew Onumajuru, Taiwo Akanni, Olusegun Adebami Autosomal recessive polycystic kidney disease (ARPKD) in a Nigerian newborn: a case report. Pan Afr Med J: 2018, 30;172 PubMed 30455801

Premature Birth


Preterm delivery and lung development.jpg

Preterm delivery and overview of related potential fetal and neonatal infections can effect lung development.[7]

After very preterm birth, the chorioamnionitis associated commensal organism is usually Ureaplasma urealyticum.[8]

Links: Chorioamnionitis | Bacterial Infection

Tracheoesophageal Fistula

(Tracheo-Oesophageal Fistula, Oesophageal Atresia) - Oesophageal Atresia with or without tracheo-oesophageal fistula

Laryngeal-tracheo-oesophageal Cleft

Laryngeal-Tracheo-Oesophageal Ceft, Type III LC, endoscopic view[9]

(LC, laryngeal cleft) A rare foregut abnormality allowing digestive tract and the airway to communicate causing chronic cough, aspiration and respiratory distress.

The downward extension of the cleft determines the classification of the abnormality,PubmedParser error: Invalid PMID, please check. (PMID: 2729823PMID2729823)[9]

  • Type 0 - submucosal cleft
  • Type I - supraglottic, interarytenoid cleft, above the vocal fold level
  • Type II - cleft extending below the vocal folds into the cricoid cartilage
  • Type III a - cleft extending through the cricoid cartilage but not into the trachea
  • Type III b - cleft extending through the cricoid cartilage and into the cervical trachea
  • Type IV - cleft extending into the thoracic trachea, potentially down to the carina

Lobar Emphysema (Overinflated Lung)

Congenital lobar emphysema
  1. There is an overinflated left upper lobe
  2. There is a collapsed lower lobe
  3. The left lung is herniating across the mediastinum

Congenital Diaphragmatic Hernia

Really a musculoskeletal abnormality, but included here due to the associated respiratory effects. Failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close allows viscera into thorax, most common (80-85%) on the left side of diaphragm. Intestine, stomach or spleen can enter the pleural cavity, compressing the lung.

Gray0391.jpg Human congenital diaphragmatic hernia.jpg
Normal Adult Diaphragm Human congenital diaphragmatic hernia[1]
Congenital diaphragmatic hernia 01.jpg
Left posterolateral diaphragmatic hernia[10]
  • A - Plain X-ray of the thorax of a newborn with CDH. There are bowel loops into the left hemi-thorax, the mediastinum is displaced to the contralateral side and the space occupied by the lung is reduced.
  • B - small bowel loops can be seen entering the thorax through the orifice.
  • C - seen after reducing the contents of the hernia.
  • D - At autopsy, extreme left lung hypoplasia and less severe right lung hypoplasia were discovered.

Australian Statistics

A recent Western Australian study[11] of congenital diaphragmatic hernia (CDH) outcomes showed:

  • 35% of live-born infants died before referral or transport.
  • population of infants reaching center represented only 40% of the total cases
  • 92% percent of postoperative infants survived beyond 1 year of age
  • 80% of infants who reached the surgical referral center
  • only 52% of live-born infants, 32% of all cases, and 16% of all prenatally diagnosed cases survived.
  • the overall mortality rate for this condition remains high
  • 33% of all cases of CDH and 49% of prenatally diagnosed fetuses underwent elective termination of pregnancy
  • the number of fetal terminations confounds the accurate assessment of the true outcomes of this condition

Links: Musculoskeletal System - Abnormalities | GeneReviews

Azygos Lobe

Lung azygos lobe in the adult.

Lung Azygos Lobe 02.jpg

Common anatomical variation occurring in about 0.5% of the population. The right lung upper lobe expands either side of the posterior cardinal. There is also some course variability of the phrenic nerve in the presence of an azygos lobe.

Congenital Laryngeal Webs

Laryngeal abnormality due to embryonic (week 10) incomplete recanalization of the laryngotracheal tube during the fetal period. Rare abnormality occuring mainly at the level of the vocal folds (glottis).

Meconium Aspiration Syndrome

Newborn X-ray Meconium aspiration syndrome

(MAS) Meconium is the gastrointestinal contents that accumulate in the intestines during the fetal period. Fetal stress in the third trimester, prior to/at/ or during parturition (birth) can lead to premature meconium discharge into the amniotic fluid and sunsequent ingestion by the fetus and damage to respiratory function. Damage to placental vessels meconium myonecrosis may also occur.

  • meconium is formed from gut and associated organ secretions as well as cells and debris from the swallowed amniotic fluid.
  • Meconium accumulates during the fetal period in the large intestine (bowel). It can be described as being a generally dark colour (green black) , sticky and odourless.
  • Normally this meconium is defaecated (passed) postnatally over the first 48 hours and then transitional stools from day 4.
  • Abnormally this meconium is defaecated in utero, due to oxygen deprivation and other stresses. Premature discharge into the amniotic sac can lead to mixing with amniotic fluid and be reswallowed by the fetus. This is meconium aspiration syndrome and can damage both the developing lungs and placental vessels.

Australian Statistics

The following Australia and New Zealand (1995 - 2002) data is from a recent (2009) study, the epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome.[12]

  • Data were gathered on all of the infants in Australia and New Zealand who were intubated and mechanically ventilated with a primary diagnosis of MAS (MASINT) between 1995 and 2002, inclusive.
  • MASINT occurred in 1061 of 2,490,862 live births (0.43 of 1000), with a decrease in incidence from 1995 to 2002.
  • A higher risk of MASINT was noted at advanced gestation, with 34% of cases born beyond 40 weeks, compared with 16% of infants without MAS.
  • Fetal distress requiring obstetric intervention was noted in 51% of cases, and 42% were delivered by cesarean section.
  • There was a striking association between low 5-minute Apgar score and MASINT.
  • Risk of MASINT was higher where maternal ethnicity was Pacific Islander or indigenous Australian and was also increased after planned home birth.
  • Uptake of exogenous surfactant, high-frequency ventilation, and inhaled nitric oxide increased considerably during the study period, with >50% of infants receiving > or =1 of these therapies by 2002.
  • Risk of air leak was 9.6% overall, with an apparent reduction to 5.3% in 2001-2002.
  • The duration of intubation remained constant throughout the study period (median: 3 days), whereas duration of oxygen therapy and length of hospital stay increased.
  • Death related to MAS occurred in 24 infants (2.5% of the MASINT cohort; 0.96 per 100,000 live births).

Newborn Respiratory Distress Syndrome

Mary Ellen Avery
Prof. Mary Ellen Avery

The historic name of "Hyaline Membrane Disease" (HMD) described the "glassy" appearance of the premature neonatal lungs due to insufficient surfactant.

Surfactant deficiency in immature lungs leads to:

  1. alveolar instability and collapse
  2. capillary leak edema
  3. hyaline membrane formation
Links: medline plus | eMedicine

Hyaline Membrane Disease History

See the recent review of Hyaline Membrane Disease (HMD) history[13] and surfactant.[14]

  • 1835 - first description in premature babies born with immature “fetal lungs.”
  • 1947 - pressure required to inflate deceased newborn lungs lower when saline was introduced into the lungs.
  • 1959 - concept that HMD due to lack of surfactant (Prof. Mary Ellen Avery).
  • 1980 - first study on endotracheal administration of surfactant in premature infants.

Surfactant Metabolism

(pulmonary surfactant metabolism dysfunctions, surfactant dysfunction disorders) For review of genetic disorders of surfactant dysfunction[15]

Mutations in the genes encoding:

  • surfactant protein B (SP-B)
  • surfactant protein C ( SP-C)
  • phospholipid transporter ABCA3

Bronchopulmonary Dysplasia

A chronic lung disease which can occur following premature birth and related lung injury. The definition of bronchopulmonary dysplasia (BPD) has in recent years changed from a severe lung injury and associated repair, to more of a disruption of lung growth in older infants.[16]

Most infants who develop BPD are born more than 10 weeks before their due dates, weigh less than 1,000 grams (about 2 pounds) at birth, and have breathing problems. Infections that occur before or shortly after birth also can contribute to BPD.

Links: NIH - NHLBI

Lung Agenesis

Agenesis of left lung.jpg

Agenesis of Left lung (X Ray)[17]

Prevalence, including the bilateral and unilateral forms, is 0.5-1.0 per 10,000 live births.

Cystic Fibrosis

UK deaths from cystic fibrosis [18]

Cystic Fibrosis (CF) is a serious genetic disease due to abnormal chloride channel synthesis (cystic fibrosis transmembrane conductance regulator, CFTR), the impact occurs postnatally. Mucus accumulates mainly in the passages of the lungs and in the pancreas.

Links: PubMed Health | OMIM | USA National Heart Lung and Blood Institute | Cystic Fibrosis Australia


List of respiratory related abnormalities Respiratory and Diaphragmatic Hernia.


  1. 1.0 1.1 Fisher JC & Bodenstein L. (2006). Computer simulation analysis of normal and abnormal development of the mammalian diaphragm. Theor Biol Med Model , 3, 9. PMID: 16483386 DOI.
  2. Kemppainen M, Lahesmaa-Korpinen AM, Kauppi P, Virtanen M, Virtanen SM, Karikoski R, Gissler M & Kirjavainen T. (2018). Maternal asthma is associated with increased risk of perinatal mortality. PLoS ONE , 13, e0197593. PMID: 29775476 DOI.
  3. Lo J, Zivanovic S, Lunt A, Alcazar-Paris M, Andradi G, Thomas M, Marlow N, Calvert S, Peacock J & Greenough A. (2018). Longitudinal assessment of lung function in extremely prematurely born children. Pediatr. Pulmonol. , 53, 324-331. PMID: 29316378 DOI.
  4. Hagadorn JI, Brownell EA, Herbst KW, Trzaski JM, Neff S & Campbell BT. (2015). Trends in treatment and in-hospital mortality for neonates with congenital diaphragmatic hernia. J Perinatol , 35, 748-54. PMID: 25950919 DOI.
  5. McFetridge L, McMorrow A, Morrison PJ & Shields MD. (2009). Surfactant Metabolism Dysfunction and Childhood Interstitial Lung Disease (chILD). Ulster Med J , 78, 7-9. PMID: 19252722
  6. Kim CJ, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, Gotsch F, Yoon BH, Chi JG & Kim JS. (2010). The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth. Mod. Pathol. , 23, 1000-11. PMID: 20348884 DOI.
  7. Jobe AH & Ikegami M. (2001). Antenatal infection/inflammation and postnatal lung maturation and injury. Respir. Res. , 2, 27-32. PMID: 11686862
  8. Goldenberg RL, Hauth JC & Andrews WW. (2000). Intrauterine infection and preterm delivery. N. Engl. J. Med. , 342, 1500-7. PMID: 10816189 DOI.
  9. 9.0 9.1 Leboulanger N & Garabédian EN. (2011). Laryngo-tracheo-oesophageal clefts. Orphanet J Rare Dis , 6, 81. PMID: 22151899 DOI.
  10. Juan A Tovar Congenital diaphragmatic hernia. Orphanet J Rare Dis: 2012, 7;1 PubMed 22214468 | Orphanet J Rare Dis.
  11. Joanne Colvin, Carol Bower, Jan E Dickinson, Jenni Sokol Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia. Pediatrics: 2005, 116(3);e356-63 PubMed 16140678
  12. Dargaville PA & Copnell B. (2006). The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome. Pediatrics , 117, 1712-21. PMID: 16651329 DOI.
  13. Aly H, Mohamed MA & Wung JT. (2017). Surfactant and continuous positive airway pressure for the prevention of chronic lung disease: History, reality, and new challenges. Semin Fetal Neonatal Med , 22, 348-353. PMID: 28818610 DOI.
  14. Obladen M. (2005). History of surfactant up to 1980. Biol. Neonate , 87, 308-16. PMID: 15985753 DOI.
  15. Susan E Wert, Jeffrey A Whitsett, Lawrence M Nogee Genetic disorders of surfactant dysfunction. Pediatr. Dev. Pathol.: 2009, 12(4);253-74 PubMed 19220077
  16. Deakins KM. (2009). Bronchopulmonary dysplasia. Respir Care , 54, 1252-62. PMID: 19712501
  17. Jentzsch NS. (2014). Unilateral pulmonary agenesis. J Bras Pneumol , 40, 322-4. PMID: 25029657
  18. Barr HL, Britton J, Smyth AR & Fogarty AW. (2011). Association between socioeconomic status, sex, and age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional study. BMJ , 343, d4662. PMID: 21862532


Gur M, Hakim F & Bentur L. (2017). Better understanding of childhood asthma, towards primary prevention - are we there yet? Consideration of pertinent literature. F1000Res , 6, 2152. PMID: 29333254 DOI.

Aly H, Mohamed MA & Wung JT. (2017). Surfactant and continuous positive airway pressure for the prevention of chronic lung disease: History, reality, and new challenges. Semin Fetal Neonatal Med , 22, 348-353. PMID: 28818610 DOI.

Clement A, Nathan N, Epaud R, Fauroux B & Corvol H. (2010). Interstitial lung diseases in children. Orphanet J Rare Dis , 5, 22. PMID: 20727133 DOI.

Thébaud B & Abman SH. (2007). Bronchopulmonary dysplasia: where have all the vessels gone? Roles of angiogenic growth factors in chronic lung disease. Am. J. Respir. Crit. Care Med. , 175, 978-85. PMID: 17272782 DOI.

Hartl D & Griese M. (2005). Interstitial lung disease in children -- genetic background and associated phenotypes. Respir. Res. , 6, 32. PMID: 15819986 DOI.


Sztanó B, Torkos A & Rovó L. (2010). The combined endoscopic management of congenital laryngeal web. Int. J. Pediatr. Otorhinolaryngol. , 74, 212-5. PMID: 20004027 DOI.

Shannon EH. (1931). THE AZYGOS LOBE OF THE LUNG. Can Med Assoc J , 24, 498-500. PMID: 20318245

Mata J, Cáceres J, Alegret X, Coscojuela P & De Marcos JA. (1991). Imaging of the azygos lobe: normal anatomy and variations. AJR Am J Roentgenol , 156, 931-7. PMID: 2017954 DOI.

Whitfield JM, Charsha DS & Chiruvolu A. (2009). Prevention of meconium aspiration syndrome: an update and the Baylor experience. Proc (Bayl Univ Med Cent) , 22, 128-31. PMID: 19381312

Speckman JM, Gamsu G & Webb WR. (1981). Alterations in CT mediastinal anatomy produced by an azygos lobe. AJR Am J Roentgenol , 137, 47-50. PMID: 6787889 DOI.

Baumgartner FJ. (2009). Thoracoscopic surgery for hyperhidrosis in the presence of congenital azygous lobe and its suspensory web. Tex Heart Inst J , 36, 44-7. PMID: 19436785

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Search Pubmed: Respiratory System Developmental Abnormalities | Tracheoesophageal Fistula | Bronchopulmonary Dysplasia | Congenital Laryngeal Webs | Hyaline Membrane Disease | Meconium Aspiration Syndrome

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