Exercise-induced laryngeal obstruction

Exercise-induced laryngeal obstruction (EILO) is a transient, reversible narrowing of the larynx that occurs during high intensity exercise. This acts to impair airflow and cause shortness of breath, stridor and often discomfort in the throat and upper chest. EILO is a very common cause of breathing difficulties in young athletic individuals but is often misdiagnosed as asthma or exercise-induced bronchoconstriction.{{cite journal |last1=Hall |first1=Andrew |last2=Thomas |first2=Mike |last3=Sandhu |first3=Guri |last4=Hull |first4=James H |title=Exercise-induced laryngeal obstruction: a common and overlooked cause of exertional breathlessness |journal=British Journal of General Practice |date=September 2016 |volume=66 |issue=650 |pages=e683–e685 |doi=10.3399/bjgp16X687001 |pmid=27563141 |pmc=5198683 }}{{cite journal |last1=Halvorsen |first1=Thomas |last2=Walsted |first2=Emil Schwarz |last3=Bucca |first3=Caterina |last4=Bush |first4=Andrew |last5=Cantarella |first5=Giovanna |last6=Friedrich |first6=Gerhard |last7=Herth |first7=Felix J.F. |last8=Hull |first8=James H. |last9=Jung |first9=Harald |last10=Maat |first10=Robert |last11=Nordang |first11=Leif |last12=Remacle |first12=Marc |last13=Rasmussen |first13=Niels |last14=Wilson |first14=Janet A. |last15=Heimdal |first15=John-Helge |title=Inducible laryngeal obstruction: an official joint European Respiratory Society and European Laryngological Society statement |journal=European Respiratory Journal |date=September 2017 |volume=50 |issue=3 |pages=1602221 |doi=10.1183/13993003.02221-2016 |pmid=28889105 |doi-access=free |hdl=10044/1/54549 |hdl-access=free }}

Causes

EILO may arise because of a relative mechanical 'insufficiency' of the laryngeal structures that should act to maintain glottic patency.

It has been proposed that a narrowing at the laryngeal inlet during the state of high airflow (e.g. when running fast), can act to cause a pressure drop across the larynx which then acts to 'pull' the laryngeal structures together. The Bernoulli principle states that increasing airflow through a tube creates increasing negative pressures within that tube.{{cite journal |last1=Røksund |first1=Ola Drange |last2=Heimdal |first2=John-Helge |last3=Olofsson |first3=Jan |last4=Maat |first4=Robert Christiaan |last5=Halvorsen |first5=Thomas |title=Larynx during exercise: the unexplored bottleneck of the airways |journal=European Archives of Oto-Rhino-Laryngology |date=September 2015 |volume=272 |issue=9 |pages=2101–2109 |doi=10.1007/s00405-014-3159-3 |pmid=25033930 |pmc=4526593 }}

Complex neuromuscular functioning is required to maintain laryngeal opening and to allow the larynx to achieve a great number of tasks (i.e. speaking, airway protection, swallowing).{{cite journal |last1=Hull |first1=James H. |last2=Backer |first2=Vibeke |last3=Gibson |first3=Peter G. |last4=Fowler |first4=Stephen J. |title=Laryngeal Dysfunction: Assessment and Management for the Clinician |journal=American Journal of Respiratory and Critical Care Medicine |date=1 November 2016 |volume=194 |issue=9 |pages=1062–1072 |doi=10.1164/rccm.201606-1249CI |pmid=27575803 |url=https://www.research.manchester.ac.uk/portal/en/publications/laryngeal-dysfunction(1dee70f4-ca6a-4a40-be0e-1083b9b9f46e).html }} It is thus also possible that EILO may arise as form a degree of neuromuscular failure.

A small heredity study indicated that an autosomal dominant model of inheritance with variable expressivity and reduced penetrance in males may be relevant; because in ten families studied, there was at least one affected person in every generation in which both parents were examined.{{cite journal |last1=Walsted |first1=Emil Schwarz |last2=Hvedstrup |first2=Jeppe |last3=Eiberg |first3=Hans |last4=Backer |first4=Vibeke |title=Heredity of supraglottic exercise-induced laryngeal obstruction |journal=European Respiratory Journal |date=August 2017 |volume=50 |issue=2 |pages=1700423 |doi=10.1183/13993003.00423-2017 |pmid=28818875 |doi-access=free }}

Further work is needed to determine if structural deficiencies in the laryngeal tissue of individuals with EILO are present.{{fact|date=September 2022}}

Mechanism

EILO is typically caused by a narrowing of the supra-glottic structures of the larynx. In severe cases, these structures, also called arytenoids, can close over to almost completely close the laryngeal inlet.{{fact|date=September 2022}}

In fewer cases, the glottic (i.e. vocal cord) structures close together and this is typically what happens during exercise-induced vocal-cord dysfunction.{{fact|date=September 2022}}

EILO develops during intense exercise and closure develops as exercise becomes more intense.{{cite journal |last1=Olin |first1=J. Tod |last2=Clary |first2=Matthew S. |last3=Fan |first3=Elizabeth M. |last4=Johnston |first4=Kristina L. |last5=State |first5=Claire M. |last6=Strand |first6=Matthew |last7=Christopher |first7=Kent L. |title=Continuous laryngoscopy quantitates laryngeal behaviour in exercise and recovery |journal=European Respiratory Journal |date=October 2016 |volume=48 |issue=4 |pages=1192–1200 |doi=10.1183/13993003.00160-2016 |pmid=27418554 |doi-access=free }}

Closure of the voice box during exercise causes increased 'loading' on the breathing system and the respiratory muscles have to work much harder.{{cite journal |last1=Walsted |first1=Emil S. |last2=Faisal |first2=Azmy |last3=Jolley |first3=Caroline J. |last4=Swanton |first4=Laura L. |last5=Pavitt |first5=Matthew J. |last6=Luo |first6=Yuan-Ming |last7=Backer |first7=Vibeke |last8=Polkey |first8=Michael I. |last9=Hull |first9=James H. |title=Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction |journal=Journal of Applied Physiology |date=1 February 2018 |volume=124 |issue=2 |pages=356–363 |doi=10.1152/japplphysiol.00691.2017 |pmid=29097629 |pmc=5867370 }}

Epidemiology

The prevalence of EILO in adolescents and young adults appears to be in the range of 5–7% in northern Europe, with some indication that EILO may be more prevalent in highly trained athletes.{{cite journal |last1=Johansson |first1=Henrik |last2=Norlander |first2=Katarina |last3=Berglund |first3=Lars |last4=Janson |first4=Christer |last5=Malinovschi |first5=Andrei |last6=Nordvall |first6=Lennart |last7=Nordang |first7=Leif |last8=Emtner |first8=Margareta |title=Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population |journal=Thorax |date=January 2015 |volume=70 |issue=1 |pages=57–63 |doi=10.1136/thoraxjnl-2014-205738 |pmid=25380758 |doi-access=free }}{{cite journal |last1=Christensen |first1=Pernille M. |last2=Thomsen |first2=S. F. |last3=Rasmussen |first3=N. |last4=Backer |first4=V. |title=Exercise-induced laryngeal obstructions: prevalence and symptoms in the general public |journal=European Archives of Oto-Rhino-Laryngology |date=September 2011 |volume=268 |issue=9 |pages=1313–1319 |doi=10.1007/s00405-011-1612-0 |pmid=21528411 |s2cid=23253671 }}{{Cite journal |last1=Ersson |first1=Karin |last2=Mallmin |first2=Elisabet |last3=Malinovschi |first3=Andrei |last4=Norlander |first4=Katarina |last5=Johansson |first5=Henrik |last6=Nordang |first6=Leif |date=December 2020 |title=Prevalence of exercise‐induced bronchoconstriction and laryngeal obstruction in adolescent athletes |journal=Pediatric Pulmonology |language=en |volume=55 |issue=12 |pages=3509–3516 |doi=10.1002/ppul.25104 |pmid=33002318 |pmc=7702091 |issn=8755-6863|doi-access=free }}

Some, but not all studies report a higher female prevalence. Thus, in a study of 94 patients diagnosed using the CLE test, average age was ~15 years, and 68% were female.{{cite journal |last1=Maat |first1=Robert Christiaan |last2=Hilland |first2=Magnus |last3=Røksund |first3=Ola Drange |last4=Halvorsen |first4=Thomas |last5=Olofsson |first5=Jan |last6=Aarstad |first6=Hans Jørgen |last7=Heimdal |first7=John-Helge |title=Exercise-induced laryngeal obstruction: natural history and effect of surgical treatment |journal=European Archives of Oto-Rhino-Laryngology |date=October 2011 |volume=268 |issue=10 |pages=1485–1492 |doi=10.1007/s00405-011-1656-1 |pmid=21643933 |pmc=3166603 }}

In athletic individuals EILO appears to be a highly prevalent cause of cough and wheeze and can co-exist with EIB. In one study, of almost 90 athletes, with unexplained respiratory symptoms, EILO was found to be present in approximately 30% of athletes, whilst EILO and EIB co-existed in one in ten.{{cite journal |last1=Nielsen |first1=Emil Walsted |last2=Hull |first2=James H. |last3=Backer |first3=Vibeke |title=High Prevalence of Exercise-Induced Laryngeal Obstruction in Athletes |journal=Medicine & Science in Sports & Exercise |date=November 2013 |volume=45 |issue=11 |pages=2030–2035 |doi=10.1249/MSS.0b013e318298b19a |pmid=23657163 |s2cid=6603638 |doi-access=free }}

This condition can co-exist with other conditions, including severe asthma.{{cite journal |last1=Hull |first1=James H. |last2=Walsted |first2=Emil S. |last3=Pavitt |first3=Matt J. |last4=Menzies-Gow |first4=Andrew |last5=Backer |first5=Vibeke |last6=Sandhu |first6=Guri |title=High Prevalence of Laryngeal Obstruction during Exercise in Severe Asthma |journal=American Journal of Respiratory and Critical Care Medicine |date=15 February 2019 |volume=199 |issue=4 |pages=538–542 |doi=10.1164/rccm.201809-1734LE |pmid=30570393 |pmc=6376624 }}

Clinical features

Key clinical features often include:{{cite journal |last1=Griffin |first1=Steffan Arthur |last2=Walsted |first2=Emil S |last3=Hull |first3=James H |title=Breathless athlete: exercise-induced laryngeal obstruction |journal=British Journal of Sports Medicine |date=September 2018 |volume=52 |issue=18 |pages=1211–1212 |doi=10.1136/bjsports-2018-099159 |pmid=29669719 |s2cid=4930495 }}
Difficulty 'catching a breath'
Wheeze or whistling sound; typically when breathing in when exercising hard
Throat or upper chest discomfort
Symptoms often start to improve from the time of exercise cessation / reducing exercise intensity
No improvement with standard asthma medication (e.g. salbutamol, albuterol).

Diagnosis

The current gold-standard means for diagnosing EILO is the continuous laryngoscopy during exercise test (CLE-test). This test involves the placement of a flexible laryngoscope via nostril, which is then secured in place and held with headgear. It allows continuous visualization of the laryngeal aperture during exercise.

The CLE test can be used during indoor treadmill or cycle-ergometer exercise but also whilst rowing or swimming{{cite journal |last1=Walsted |first1=Emil S. |last2=Swanton |first2=Laura L. |last3=van van Someren |first3=Ken |last4=Morris |first4=Tessa E. |last5=Furber |first5=Matthew |last6=Backer |first6=Vibeke |last7=Hull |first7=James H. |title=Laryngoscopy during swimming: A novel diagnostic technique to characterize swimming-induced laryngeal obstruction: Laryngoscopy During Swimming |journal=The Laryngoscope |date=October 2017 |volume=127 |issue=10 |pages=2298–2301 |doi=10.1002/lary.26532 |pmid=28236311 |s2cid=45634351 }} or exercising outdoors.{{cite journal |last1=Hull |first1=James H. |last2=Walsted |first2=Emil S. |last3=Orton |first3=Christopher M. |last4=Williams |first4=Parris |last5=Ward |first5=Simon |last6=Pavitt |first6=Mathew J. |title=Feasibility of portable continuous laryngoscopy during exercise testing |journal=ERJ Open Research |date=February 2019 |volume=5 |issue=1 |doi=10.1183/23120541.00219-2018 |pmid=30740460 |pmc=6360209 }}

The examiner visually evaluates the relative change of the laryngeal inlet in the patient throughout the CLE-test. One common grading system uses 4 steps (0-3) on glottic and supraglottic level respectively. Grades 0-1 are considered normal, whereas grades 2-3 on either or both levels are consistent with EILO.{{cite journal |last1=Røksund |first1=Ola Drange |last2=Maat |first2=Robert Christiaan |last3=Heimdal |first3=John Helge |last4=Olofsson |first4=Jan |last5=Skadberg |first5=Britt Torunn |last6=Halvorsen |first6=Thomas |title=Exercise induced dyspnea in the young. Larynx as the bottleneck of the airways |journal=Respiratory Medicine |date=1 December 2009 |volume=103 |issue=12 |pages=1911–1918 |doi=10.1016/j.rmed.2009.05.024 |pmid=19782550 |hdl=1956/5337 |hdl-access=free }}

There is a need to identify other less-invasive means of making a secure diagnosis.

Treatment

The current mainstay of treatment is therapy-based. Specialist breathing techniques, most commonly termed biphasic breathing techniques or EILOBI are recommended to reduce turbulent inspiratory airflow and thus reduce chance of laryngeal closure.{{cite journal |last1=Johnston |first1=Kristina L. |last2=Bradford |first2=Hannah |last3=Hodges |first3=Heather |last4=Moore |first4=Camille M. |last5=Nauman |first5=Emily |last6=Olin |first6=J. Tod |title=The Olin EILOBI Breathing Techniques: Description and Initial Case Series of Novel Respiratory Retraining Strategies for Athletes with Exercise-Induced Laryngeal Obstruction |journal=Journal of Voice |date=November 2018 |volume=32 |issue=6 |pages=698–704 |doi=10.1016/j.jvoice.2017.08.020 |pmid=29050661 |s2cid=36324540 }}

Direct laryngeal visualisation during exercise to deliver biofeedback has been employed with success.{{cn|date=June 2020}}

The place of inspiratory muscle training (IMT) is yet to be defined in EILO therapy.{{fact|date=September 2022}}

Surgical treatment with supraglottopasty has also been utilised with success.{{cite journal |last1=Heimdal |first1=John-Helge |last2=Maat |first2=Robert |last3=Nordang |first3=Leif |title=Surgical Intervention for Exercise-Induced Laryngeal Obstruction |journal=Immunology and Allergy Clinics of North America |date=May 2018 |volume=38 |issue=2 |pages=317–324 |doi=10.1016/j.iac.2018.01.005 |pmid=29631739 }}

Avoiding unnecessary treatment with asthma inhalers is important.{{cn|date=June 2020}}