Shortness of breath

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Shortness of breath
Other names: Dyspnea, dyspnoea, breathlessness, difficulty of breathing, respiratory distress
SymptomsFeverCoughSOB (cropped).jpg
Pronunciation
  • Dyspnea: /dɪspˈniːə/
SpecialtyPulmonology
TypesAcute, chronic[1]
CausesCommon: Common cold, smoking, overweight[2]
Serious: Asthma, pneumonia, cardiac ischemia, pulmonary embolism, heart failure, chronic obstructive pulmonary disease, anemia[1]
FrequencyCommon[1]

Shortness of breath (SOB), also known as dyspnea, is the feeling of not being able to breathe well enough.[3] This may include an increased work to breathe, chest tightness, unsatisfied breathing, or the feeling of not getting enough air.[4] Associated symptoms may include cough, sore throat, pain with breathing in, and swelling of the legs.[1] Nail clubbing may occur in those with low oxygen levels of long duration.[1]

Shortness of breath is a normal symptom of heavy exercise but may represents an underlying disease if it occurs unexpectedly.[5] Common causes include the common cold, smoking, and being overweight.[2] Serious causes may relate to the lungs such as asthma, pneumonia, pulmonary embolism, pneumothorax, and chronic obstructive pulmonary disease; heart such as cardiac ischemia, heart failure, cardiac tamponade, and pulmonary hypertension; or other systems such as anemia, chest wall trauma, and sepsis.[1] Other causes may include panic attacks and hyperventilation syndrome.[2][1]

Treatment typically depends on the underlying cause.[1][6] Assessment begins with examination of airway, breathing, and circulation.[5] If the person is stable this should than be followed by a complete examination.[1] Shortness of breath is a common complaint.[1]

Definition

The American Thoracic Society defines dyspnea as: "A subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity."[7] Other definitions describe it as "difficulty in breathing",[8] "disordered or inadequate breathing",[9] "uncomfortable awareness of breathing",[10] and as the experience of "breathlessness" (which may be either acute or chronic).[5][6][11]

Differential diagnosis

While shortness of breath is generally caused by disorders of the cardiac or respiratory system, other systems such as neurological,[12] musculoskeletal, endocrine, hematologic, and psychiatric may be the cause.[13] DiagnosisPro, an online medical expert system, listed 497 distinct causes in October 2010.[14] The most common cardiovascular causes are acute myocardial infarction and congestive heart failure while common pulmonary causes include chronic obstructive pulmonary disease, asthma, pneumothorax, pulmonary edema and pneumonia.[5] On a pathophysiological basis the causes can be divided into: (1) an increased awareness of normal breathing such as during an anxiety attack, (2) an increase in the work of breathing and (3) an abnormality in the ventilatory system.[12]

The speed of onset and the duration may be useful in helping to determine the cause. Sudden onset is usually connected with laryngeal edema, bronchospasm, myocardial infarction, pulmonary embolism, or pneumothorax. People with COPD and idiopathic pulmonary fibrosis generally have a gradual progression with initial presess with exertion, punctuated by acute worsening. In contrast, most asthmatics do not have daily symptoms, but have intermittent episodes of shortness of breath, cough, and chest tightness that are usually associated with specific triggers, such as an upper respiratory tract infection or exposure to allergens.[15]

Lungs

Asthma

Asthma is the most common reason for presenting to the emergency room with shortness of breath.[5] It is the most common lung disease in both developing and developed countries affecting about 5% of the population.[5] Other symptoms include wheezing, tightness in the chest, and a non productive cough.[5] Inhaled corticosteroids are the preferred treatment for children, however these drugs can reduce the growth rate.[16] Acute symptoms are treated with short-acting bronchodilators.

Chronic obstructive pulmonary disease

People with chronic obstructive pulmonary disease (COPD) frequently have chronic shortness of breath and a chronic productive cough.[5] An acute exacerbation presents with increased shortness of breath and sputum production.[5] COPD is a risk factor for pneumonia; thus this condition should be ruled out.[5] In an acute exacerbation treatment is with a combination of anticholinergics, beta2-adrenoceptor agonists, steroids and possibly positive pressure ventilation.[5]

Pneumonia

The symptoms of pneumonia are fever, productive cough, shortness of breath, and pleuritic chest pain.[5] Inspiratory crackles may be heard on exam.[5] A chest x-ray can be useful to differentiate pneumonia from congestive heart failure.[5] As the cause is usually a bacterial infection, antibiotics are typically used for treatment.[5]

People that have been infected by COVID-19 may have symptoms such as a fever, dry cough, loss of smell and taste, or shortness of breath.

Pneumothorax

Pneumothorax presents typically with pleuritic chest pain of acute onset and shortness of breath not improved with oxygen.[5] Physical findings may include absent breath sounds on one side of the chest, jugular venous distension, and tracheal deviation.[5]

Pulmonary embolism

Pulmonary embolism classically presents with an acute onset of shortness of breath.[5] Other presenting symptoms include pleuritic chest pain, cough, hemoptysis, and fever.[5] Risk factors include deep vein thrombosis, recent surgery, cancer, and previous thromboembolism.[5] It must always be considered in those with acute onset of shortness of breath owing to its high risk of mortality.[5] Diagnosis, however, may be difficult[5] and Wells Score is often used to assess the clinical probability. Treatment, depending on severity of symptoms, typically starts with anticoagulants; the presence of ominous signs (low blood pressure) may warrant the use of thrombolytic drugs.[5]

Heart

Acute coronary syndrome

Acute coronary syndrome frequently presents with retrosternal chest discomfort and difficulty catching the breath.[5] It however may atypically present with shortness of breath alone.[17] Risk factors include old age, smoking, hypertension, hyperlipidemia, and diabetes.[17] An electrocardiogram and cardiac enzymes are important both for diagnosis and directing treatment.[17] Treatment involves measures to decrease the oxygen requirement of the heart and efforts to increase blood flow.[5]

Heart failure

Heart failure frequently presents with shortness of breath with exertion, orthopnea, and paroxysmal nocturnal dyspnea.[5] It affects between 1–2% of the general United States population and occurs in 10% of those over 65 years old.[5][17] Risk factors for acute decompensation include high dietary salt intake, medication noncompliance, cardiac ischemia, abnormal heart rhythms, kidney failure, pulmonary emboli, hypertension, and infections.[17] Treatment efforts are directed towards decreasing lung congestion.[5]

Tamponade

Cardiac tamponade presents with shortness of breath, fast heart rate, elevated jugular venous pressure, and pulsus paradoxus.[18] The gold standard for diagnosis is ultrasound.[18]

Chest wall

Neuromuscular causes may include chest trauma with fracture or flail chest, massive obesity, kyphoscoliosis, central nervous system or spinal cord dysfunction, phrenic nerve paralysis, myopathy, and neuropathy.[1]

Other

Anemia that develops gradually usually presents with exertional dyspnea, fatigue, weakness, and tachycardia.[18] It may lead to heart failure.[18] Anaemia is often a cause of dyspnea. Menstruation, particularly if excessive, can contribute to anaemia and to consequential dyspnea in women. Headaches are also a symptom of dyspnea in patients suffering from anaemia. Some patients report a numb sensation in their head, and others have reported blurred vision caused by hypotension behind the eye due to a lack of oxygen and pressure; these patients have also reported severe head pains, many of which lead to permanent brain damage. Symptoms can include loss of concentration, focus, fatigue, language faculty impairment and memory loss.[19][citation needed]

Other important or common causes of shortness of breath include anaphylaxis, interstitial lung disease, panic attacks,[6][13][18] and pulmonary hypertension. Also, around 2/3 of women experience shortness of breath as a part of a normal pregnancy.[9]

Anaphylaxis typically begins over a few minutes in a person with a previous history of the same.[6] Other symptoms include urticaria, throat swelling, and gastrointestinal upset.[6] The primary treatment is epinephrine.[6]

Interstitial lung disease presents with gradual onset of shortness of breath typically with a history of a predisposing environmental exposure.[13] Shortness of breath is often the only symptom in those with tachydysrhythmias.[17]

Panic attacks typically present with hyperventilation, sweating, and numbness.[6] They are however a diagnosis of exclusion.[13]

Neurological conditions such as spinal cord injury, phrenic nerve injuries, Guillain–Barré syndrome, amyotrophic lateral sclerosis, multiple sclerosis and muscular dystrophy can all cause an individual to experience shortness of breath.[12] Shortness of breath can also occur as a result of vocal cord dysfunction (VCD).[20]

Pathophysiology

Different physiological pathways may lead to shortness of breath including via ASIC chemoreceptors, mechanoreceptors, and lung receptors.[17]

It is thought that three main components contribute to dyspnea: afferent signals, efferent signals, and central information processing. It is believed the central processing in the brain compares the afferent and efferent signals; and dyspnea results when a "mismatch" occurs between the two: such as when the need for ventilation (afferent signaling) is not being met by physical breathing (efferent signaling).[21]

Afferent signals are sensory neuronal signals that ascend to the brain. Afferent neurons significant in dyspnea arise from a large number of sources including the carotid bodies, medulla, lungs, and chest wall. Chemoreceptors in the carotid bodies and medulla supply information regarding the blood gas levels of O2, CO2 and H+. In the lungs, juxtacapillary (J) receptors are sensitive to pulmonary interstitial edema, while stretch receptors signal bronchoconstriction. Muscle spindles in the chest wall signal the stretch and tension of the respiratory muscles. Thus, poor ventilation leading to hypercapnia, left heart failure leading to interstitial edema (impairing gas exchange), asthma causing bronchoconstriction (limiting airflow) and muscle fatigue leading to ineffective respiratory muscle action could all contribute to a feeling of dyspnea.[21]

Efferent signals are the motor neuronal signals descending to the respiratory muscles. The most important respiratory muscle is the diaphragm. Other respiratory muscles include the external and internal intercostal muscles, the abdominal muscles and the accessory breathing muscles.

As the brain receives its plentiful supply of afferent information relating to ventilation, it is able to compare it to the current level of respiration as determined by the efferent signals. If the level of respiration is inappropriate for the body's status then dyspnea might occur. There is also a psychological component to dyspnea, as some people may become aware of their breathing in such circumstances but not experience the typical distress of dyspnea.[21]

Evaluation

mMRC breathlessness scale
Grade Degree of dyspnea
0 no dyspnea except with strenuous exercise
1 dyspnea when walking up an incline or hurrying on the level
2 walks slower than most on the level, or stops after 15 minutes of walking on the level
3 stops after a few minutes of walking on the level
4 with minimal activity such as getting dressed, too dyspneic to leave the house

The initial approach to evaluation begins by assessment of the airway, breathing, and circulation followed by a medical history and physical examination.[5] Signs that represent significant severity include hypotension, hypoxemia, tracheal deviation, altered mental status, unstable dysrhythmia, stridor, intercostal indrawing, cyanosis, tripod positioning, pronounced use of accessory muscles (sternocleidomastoid, scalenes) and absent breath sounds.[13]

A number of scales may be used to quantify the degree of shortness of breath.[22] It may be subjectively rated on a scale from 1 to 10 with descriptors associated with the number (The Modified Borg Scale).[22] Alternatively a scale such as the MRC breathlessness scale might be used – it suggests five grades of dyspnea based on the circumstances in which it arises.[23]

Blood tests

A number of labs may be helpful in determining the cause of shortness of breath. D-dimer, while useful to rule out a pulmonary embolism in those who are at low risk, is not of much value if it is positive, as it may be positive in a number of conditions that lead to shortness of breath.[17] A low level of brain natriuretic peptide is useful in ruling out congestive heart failure; however, a high level, while supportive of the diagnosis, could also be due to advanced age, kidney failure, acute coronary syndrome, or a large pulmonary embolism.[17]

Imaging

A chest x-ray is useful to confirm or rule out a pneumothorax, pulmonary edema, or pneumonia.[17] Spiral computed tomography with intravenous radiocontrast is the imaging study of choice to evaluate for pulmonary embolism.[17]

Treatment

The primary treatment of shortness of breath is directed at its underlying cause.[6] Extra oxygen is effective in those with hypoxia; however, this has no effect in those with normal blood oxygen saturations.[10][24]

Physiotherapy

Individuals can benefit from a variety of physical therapy interventions.[25] Persons with neurological/neuromuscular abnormalities may have breathing difficulties due to weak or paralyzed intercostal, abdominal and/or other muscles needed for ventilation.[26] Some physical therapy interventions for this population include active assisted cough techniques,[27] volume augmentation such as breath stacking,[28] education about body position and ventilation patterns[29] and movement strategies to facilitate breathing.[28] Pulmonary rehabilitation may alleviate symptoms in some people, such as those with COPD, but will not cure the underlying disease.[30][31] Fan therapy to the face has been shown to relieve shortness of breath in patients with a variety of advanced illnesses including cancer.[32] The mechanism of action is thought to be stimulation of the trigeminal nerve.

End of life care

Immediate release opioids are beneficial in rapidly reducing the symptom of shortness of breath due to both cancer and non cancer causes;[10][33] long-acting or sustained-release opioids are also used to prevent and treatment of shortness of breath in palliative setting. There is a lack of evidence to recommend midazolam, nebulised opioids, the use of gas mixtures, or cognitive-behavioral therapy.[34]

Epidemiology

Shortness of breath is the primary reason 3.5% of people present to the emergency department in the United States. Of these individuals, approximately 51% are admitted to the hospital and 13% are dead within a year.[35] Some studies have suggested that up to 27% of people suffer from dyspnea,[36] while in dying patients 75% will experience it.[21] Acute shortness of breath is the most common reason people requiring palliative care visit an emergency department.[10]

Etymology and pronunciation

English dyspnea comes from Latin dyspnoea, from Greek dyspnoia, from dyspnoos, which literally means "disordered breathing".[13] Its combining forms (dys- + -pnea) are familiar from other medical words, such as dysfunction (dys- + function) and apnea (a- + -pnea). The most common pronunciation in medical English is /dɪspˈnə/ disp-NEE, with the p expressed and the stress on the /niː/ syllable. But pronunciations with a silent p in pn (as also in pneumo-) are common (/dɪsˈnə/ or /ˈdɪsniə/),[37] as are those with the stress on the first syllable[37] (/ˈdɪspniə/ or /ˈdɪsniə/).

In English, the various -pnea-suffixed words commonly used in medicine do not follow one clear pattern as to whether the first syllable or the /niː/ syllable is stressed; the p is usually expressed but is sometimes silent. The following collation shows the preponderance of how major dictionaries transcribe them (less-used variants are omitted):

Group Term Combining forms Preponderance of transcriptions (major dictionaries)
good eupnea eu- + -pnea /jpˈnə/ yoop-NEE[38][39][37][40]
bad dyspnea dys- + -pnea /dɪspˈnə/ disp-NEE,[39][40][41] /ˈdɪspniə/ DISP-nee-ə[38][37]
fast tachypnea tachy- + -pnea /ˌtækɪpˈnə/ TAK-ip-NEE[38][39][37][40][41]
slow bradypnea brady- + -pnea /ˌbrdɪpˈnə/ BRAY-dip-NEE[39][37][40]
upright orthopnea ortho- + -pnea /ɔːrˈθɒpniə/ or-THOP-nee-ə,[39][37][41][38]: audio  /ɔːrθəpˈnə/ or-thəp-NEE[37][38]: print 
supine platypnea platy- + -pnea /pləˈtɪpniə/ plə-TIP-nee-ə[38][39]
excessive hyperpnea hyper- + -pnea /ˌhpərpˈnə/ HY-pərp-NEE[38][39][37][40]
insufficient hypopnea hypo- + -pnea /hˈpɒpniə/ hy-POP-nee-ə,[38][39][40][41] /ˌhpəpˈnə/ HY-pəp-NEE[37][40]
absent apnea a- + -pnea /ˈæpniə/ AP-nee-ə,[38][39][37][40][41]: US  /æpˈnə/ ap-NEE[37][40][41]: UK 

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Hashmi, MF; Modi, P; Sharma, S (January 2020). "Dyspnea". PMID 29763140. {{cite journal}}: Cite journal requires |journal= (help)
  2. 2.0 2.1 2.2 "Shortness of breath". nhs.uk. 19 October 2017. Archived from the original on 22 October 2020. Retrieved 17 October 2020.
  3. Vaz, Mario; Kurpad, Anura; Raj, Tony (2020). Guyton & Hall Textbook of Medical Physiology_3rd SAE-E-book: Third South Asia Edition. Elsevier Health Sciences. p. 416. ISBN 978-81-312-5774-6. Archived from the original on 2021-08-29. Retrieved 2020-10-17.
  4. Donald A. Mahler; Denis E. O'Donnell (20 January 2014). Dyspnea: Mechanisms, Measurement, and Management, Third Edition. CRC Press. p. 3. ISBN 978-1-4822-0869-6. Archived from the original on 1 August 2020. Retrieved 1 February 2016.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 5.26 5.27 5.28 Shiber JR, Santana J (May 2006). "Dyspnea". Med. Clin. North Am. 90 (3): 453–79. doi:10.1016/j.mcna.2005.11.006. PMID 16473100.
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 Zuberi, T.; et al. (2009). "Acute breathlessness in adults". InnovAiT. 2 (5): 307–15. doi:10.1093/innovait/inp055.
  7. American Heart Society (1999). "Dyspnea mechanisms, assessment, and management: a consensus statement". American Journal of Respiratory and Critical Care Medicine. 159 (1): 321–340. doi:10.1164/ajrccm.159.1.ats898. PMID 9872857.
  8. TheFreeDictionary Archived 2019-06-05 at the Wayback Machine, retrieved on Dec 12, 2009. Citing:The American Heritage Dictionary of the English Language, Fourth Edition by Houghton Mifflin Company. Updated in 2009. Ologies & -Isms. The Gale Group 2008
  9. 9.0 9.1 "UpToDate Inc". Archived from the original on 2021-08-29.
  10. 10.0 10.1 10.2 10.3 Schrijvers D, van Fraeyenhove F (2010). "Emergencies in palliative care". Cancer J. 16 (5): 514–20. doi:10.1097/PPO.0b013e3181f28a8d. PMID 20890149.
  11. "dyspnea – General Practice Notebook". Archived from the original on 2011-06-13.
  12. 12.0 12.1 12.2 Frownfelter, Donna; Dean, Elizabeth (2006). "8". In Willy E. Hammon III (ed.). Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier. p. 139.
  13. 13.0 13.1 13.2 13.3 13.4 13.5 Sarkar S, Amelung PJ (September 2006). "Evaluation of the dyspneic patient in the office". Prim. Care. 33 (3): 643–57. doi:10.1016/j.pop.2006.06.007. PMID 17088153.
  14. "Archived copy". Archived from the original on 2010-11-16. Retrieved 2012-08-23.{{cite web}}: CS1 maint: archived copy as title (link)
  15. D. L. Kasper et al. (ed), Harrison's Principles of Internal Medicine, 20th edition (2018), p. 1943
  16. "How Is Asthma Treated and Controlled?". Archived from the original on 2012-09-04.
  17. 17.00 17.01 17.02 17.03 17.04 17.05 17.06 17.07 17.08 17.09 17.10 Torres M, Moayedi S (May 2007). "Evaluation of the acutely dyspneic elderly patient". Clin. Geriatr. Med. 23 (2): 307–25, vi. doi:10.1016/j.cger.2007.01.007. PMID 17462519.
  18. 18.0 18.1 18.2 18.3 18.4 Wills CP, Young M, White DW (February 2010). "Pitfalls in the evaluation of shortness of breath". Emerg. Med. Clin. North Am. 28 (1): 163–81, ix. doi:10.1016/j.emc.2009.09.011. PMID 19945605.
  19. "Anemia Affects Body...And Maybe The Mind". Johns Hopkins medicine. 2006. Archived from the original on 21 October 2020. Retrieved 15 May 2020.
  20. Ibrahim, Wanis H.; Gheriani, Heitham A.; Almohamed, Ahmed A.; Raza, Tasleem (2007-03-01). "Paradoxical vocal cord motion disorder: past, present and future". Postgraduate Medical Journal. 83 (977): 164–172. doi:10.1136/pgmj.2006.052522. ISSN 1469-0756. PMC 2599980. PMID 17344570. Archived from the original on 2016-11-08.
  21. 21.0 21.1 21.2 21.3 Harrison's Principles of Internal Medicine (Kasper DL, Fauci AS, Longo DL, et al. (eds)) (16th ed.). New York: McGraw-Hill.
  22. 22.0 22.1 Saracino A (October 2007). "Review of dyspnoea quantification in the emergency department: is a rating scale for breathlessness suitable for use as an admission prediction tool?". Emerg Med Australas. 19 (5): 394–404. doi:10.1111/j.1742-6723.2007.00999.x. PMID 17919211.
  23. Stenton C (2008). "The MRC breathless scale". Occup Med. 58 (3): 226–7. doi:10.1093/occmed/kqm162. PMID 18441368.
  24. Abernethy AP; McDonald CF; Frith PA; et al. (September 2010). "Effect of palliative oxygen versus medical (room) air in relieving breathlessness in patients with refractory dyspnea: a double-blind randomized controlled trial". Lancet. 376 (9743): 784–93. doi:10.1016/S0140-6736(10)61115-4. PMC 2962424. PMID 20816546.
  25. Frownfelter, Donna; Dean, Elizabeth (2006). "8". In Willy E. Hammon III (ed.). Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier.
  26. Frownfelter, Donna; Dean, Elizabeth (2006). "22". In Donna Frownfelter; Mary Massery (eds.). Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier. p. 368.
  27. Frownfelter, Donna; Dean, Elizabeth (2006). "22". In Donna Frownfelter; Mary Massery (eds.). Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier. pp. 368–371.
  28. 28.0 28.1 Frownfelter, Donna; Dean, Elizabeth (2006). "32". Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier. pp. 569–581.
  29. Frownfelter, Donna; Dean, Elizabeth (2006). "23". In Donna Frownfelter; Mary Massery (eds.). Cardiovascular and Pulmonary Physical Therapy. Vol. 4. Mosby Elsevier.
  30. Puhan, Milo A.; Gimeno-Santos, Elena; Cates, Christopher J.; Troosters, Thierry (2016-12-08). "Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews. 12: CD005305. doi:10.1002/14651858.CD005305.pub4. ISSN 1469-493X. PMC 6463852. PMID 27930803.
  31. Zainuldin, Rahizan; Mackey, Martin G.; Alison, Jennifer A. (2011-11-09). "Optimal intensity and type of leg exercise training for people with chronic obstructive pulmonary disease". The Cochrane Database of Systematic Reviews (11): CD008008. doi:10.1002/14651858.CD008008.pub2. ISSN 1469-493X. PMID 22071841.
  32. Matsushima, Eisuke; Inoguchi, Hironobu; Uchitomi, Yosuke; Zenda, Sadamoto; Ogawa, Asao; Kinoshita, Hiroya; Sekimoto, Asuko; Kobayashi, Masamitsu; Yamaguchi, Takuhiro (2018-10-01). "Fan Therapy Is Effective in Relieving Dyspnea in Patients With Terminally Ill Cancer: A Parallel-Arm, Randomized Controlled Trial". Journal of Pain and Symptom Management. 56 (4): 493–500. doi:10.1016/j.jpainsymman.2018.07.001. ISSN 0885-3924. PMID 30009968. Archived from the original on 2021-08-29. Retrieved 2019-05-11.
  33. Naqvi F, Cervo F, Fields S (August 2009). "Evidence-based review of interventions to improve palliation of pain, dyspnea, depression". Geriatrics. 64 (8): 8–10, 12–4. PMID 20722311.
  34. DiSalvo, WM.; Joyce, MM.; Tyson, LB.; Culkin, AE.; Mackay, K. (Apr 2008). "Putting evidence into practice: evidence-based interventions for cancer-related dyspnea" (PDF). Clin J Oncol Nurs. 12 (2): 341–52. doi:10.1188/08.CJON.341-352. PMID 18390468.[permanent dead link]
  35. Stephen J. Dubner; Steven D. Levitt (2009). SuperFreakonomics: Tales of Altruism, Terrorism, and Poorly Paid Prostitutes. New York: William Morrow. pp. 77. ISBN 978-0-06-088957-9.
  36. Murray and Nadel's Textbook of Respiratory Medicine, 4th Ed. Robert J. Mason, John F. Murray, Jay A. Nadel, 2005, Elsevier
  37. 37.00 37.01 37.02 37.03 37.04 37.05 37.06 37.07 37.08 37.09 37.10 37.11 Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster, archived from the original on 2020-10-10, retrieved 2015-04-21.
  38. 38.0 38.1 38.2 38.3 38.4 38.5 38.6 38.7 38.8 Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier, archived from the original on 2014-01-11, retrieved 2016-09-21.
  39. 39.0 39.1 39.2 39.3 39.4 39.5 39.6 39.7 39.8 Wolters Kluwer, Stedman's Medical Dictionary, Wolters Kluwer, archived from the original on 2015-09-25.
  40. 40.0 40.1 40.2 40.3 40.4 40.5 40.6 40.7 40.8 Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt, archived from the original on 2015-09-25.
  41. 41.0 41.1 41.2 41.3 41.4 41.5 Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press, archived from the original on 2014-10-22.

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