When the ability to cough is impaired, secretion clearance may be assisted and augmented with mechanical insufflation-exsufflation (MI-E). In some individuals, the efficacy of MI-E may be hampered by counterproductive upper airway reactions, where the airways close in response to positive pressures. To fully utilize the therapeutic potential inherent in the MI-E technology, we need a better understanding of the pathophysiology behind these untoward reactions. There is increasing interest in monitoring and measuring upper airway responses to MI-E and how such information can be used to optimize MI-E settings. The purpose of this narrative review is to increase the theoretical understanding of the larynx as a respiratory organ, summarize the current literature in the area, and provide insight into how this knowledge can affect current clinical practice.
FinkJB. Forced expiratory technique, directed cough, and autogenic drainage. Respir Care, 2007; 52(9):1210-1221.
2.
LawsonTV, HarrisRS. Assessment of the mechanical efficiency of coughing in healthy young adults. Clin Sci, 1967; 33(1):209-224.
3.
ToussaintM, ChatwinM, GonzalesJ, BerlowitzDJ. ENMC Respiratory Therapy Consortium. 228th ENMC International Workshop: airway clearance techniques in neuromuscular disorders. Naarden, The Netherlands, 3–5 Mar, 2017. Neuromuscul Disord, 2018; 28(3):289-298.
4.
BarachAL, BeckGJ. Exsufflation with negative pressure; physiologic and clinical studies in poliomyelitis, bronchial asthma, pulmonary emphysema, and bronchiectasis. AMA Arch Intern Med, 1954; 93(6):825-841.
5.
MiskeLJ, HickeyEM, KolbSM, WeinerDJ, PanitchHB. Use of the mechanical in-exsufflator in pediatric patients with neuromuscular disease and impaired cough. Chest, 2004; 125(4):1406-1412.
6.
BachJR. Mechanical insufflation-exsufflation: comparison of peak expiratory flows with manually assisted and unassisted coughing techniques. Chest, 1993; 104(5):1553-1562.
7.
BarachAL. The application of pressure, including exsufflation, in pulmonary emphysema. Am J Surg, 1955; 89(2):372-382.
8.
WilliamsEK, HoladayDA. The use of exsufflation with negative pressure in postoperative patients. Am J Surg, 1955; 90(4):637-640.
9.
FaurouxB, GuillemotN, AubertinG, NathanN, LabitA, ClementA, LofasoF. Physiologic benefits of mechanical insufflation-exsufflation in children with neuromuscular diseases. Chest, 2008; 133(1):161-168.
10.
ChatwinM, RossE, HartN, NickolAH, PolkeyMI, SimondsAK. Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J, 2003; 21(3):502-508.
11.
Gomez-MerinoE, BachJR. Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechanically assisted coughing. Am J Phys Med Rehabil, 2002; 81(6):411-415.
12.
ChatwinM, BushA, SimondsAK. Outcome of goal-directed non-invasive ventilation and mechanical insufflation/exsufflation in spinal muscular atrophy type I. Arch Dis Child, 2011; 96(5):426-432.
13.
ChenTH, LiangWC, ChenIC, LiuYC, HsuJH, JongYJ. Combined noninvasive ventilation and mechanical insufflator-exsufflator for acute respiratory failure in patients with neuromuscular disease: effectiveness and outcome predictors. Ther Adv Respir Dis, 2019; 13:1753466619875928.
14.
TerziN, GuerinC, GonçalvesMR. What's new in management and clearing of airway secretions in ICU patients? It is time to focus on cough augmentation. Intensive Care Med, 2019; 45(6):865-868.
15.
GonçalvesMR, HonradoT, WinckJC, PaivaJA. Effects of mechanical insufflation-exsufflation in preventing respiratory failure after extubation: a randomized controlled trial. Crit Care, 2012; 16(2):R48.
16.
RoseL, AdhikariNK, LeasaD, FergussonDA, McKimD. Cough augmentation techniques for extubation or weaning critically ill patients from mechanical ventilation. Cochrane Database Syst Rev, 2017; 1:CD011833.
17.
SiriwatR, DeerojanawongJ, SritippayawanS, HantragoolS, CheanprapaiP. Mechanical insufflation-exsufflation versus conventional chest physiotherapy in children with cerebral palsy. Respir Care, 2018; 63(2):187-193.
18.
HeYL, LiaoD, KangH, KeC, ChenY, LiuS, et al. Comparison of mechanical insufflation-exsufflation and percussors in the treatment of lung infections for children with cerebral palsy. J Pediatr Resp Dis, 2013; 9:40-47.
19.
ChatwinM, SimondsAK. Long-term mechanical insufflation-exsufflation cough assistance in neuromuscular disease: patterns of use and lessons for application. Respir Care, 2020; 65(2):135-143.
20.
HovB, AndersenT, ToussaintM, VollsæterM, MikalsenIB, IndrekvamS, et al. Prevalence of long-term mechanical insufflation-exsufflation in children with neurological conditions: a population-based study. Dev Med Child Neurol, 2021; 63(5):537-544.
21.
AllenJE, O'LearyEL. Considerations for chest clearance and cough augmentation in severe bulbar dysfunction: a case study. Can J Respir Ther, 2018; 54(3):66-70.
22.
PradatPF, BernardE, CorciaP, CouratierP, JublancC, QuerinG, et al. The French national protocol for Kennedy's disease (SBMA): consensus diagnostic and management recommendations. Orphanet J Rare Dis, 2020; 15(1):90.
23.
AndersenT, SandnesA, BrekkaAK, HillandM, ClemmH, FondenesO, et al. Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis. Thorax, 2017; 72(3):221-229.
24.
AndersenTM, SandnesA, FondenesO, NilsenRM, TysnesOB, HeimdalJH, et al. Laryngeal responses to mechanically assisted cough in progressing amyotrophic lateral sclerosis. Respir Care, 2018; 63(5):538-549.
25.
SanchoJ, ServeraE, DíazJ, MarínJ. Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis. Chest, 2004; 125(4):1400-1405.
26.
MustfaN, AielloM, LyallRA, NikoletouD, OlivieriD, LeighPN, et al. Cough augmentation in amyotrophic lateral sclerosis. Neurology, 2003; 61(9):1285-1287.
27.
RafiqMK, BradburnM, ProctorAR, BillingsCG, BianchiS, McDermottCJ, et al. A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener, 2015; 16(7-8):448-455.
28.
BachJR. Amyotrophic lateral sclerosis: predictors for prolongation of life by noninvasive respiratory aids. Arch Phys Med Rehabil, 1995; 76(9):828-832.
29.
HanayamaK, IshikawaY, BachJR. Amyotrophic lateral sclerosis: successful treatment of mucous plugging by mechanical insufflation-exsufflation. Am J Phys Med Rehabil, 1997; 76(4):338-339.
30.
Physiology and phylogeny of the larynx and trachea. In: SandhuGS, Reza NouraeiSA. editors. Laryngeal and tracheobronchial stenosis. San Diego: Plural Publishing; 2016:27-40.
31.
HullJH, BackerV, GibsonPG, FowlerSJ. Laryngeal dysfunction: assessment and management for the clinician. Am J Respir Crit Care Med, 2016; 194(9):1062-1072.
32.
SteinJF. Why did language develop?. Int J Pediatr Otorhinolaryngol, 2003; 67(Suppl 1):S131-S135.
33.
FerrisBGJr, MeadJ, OpieLH. Partitioning of respiratory flow resistance in man. J Appl Physiol, 1964; 19:653-658.
34.
BartlettDJr.. Respiratory functions of the larynx. Physiol Rev, 1989; 69(1):33-57.
35.
BaierH, WannerA, ZarzeckiS, SacknerMA. Relationships among glottis opening, respiratory flow, and upper airway resistance in humans. J Appl Physiol Respir Environ Exerc Physiol, 1977; 43(4):603-611.
36.
DarwinC, BynumWF. The origin of species by means of natural selection: the preservation of favored races in the struggle for life. New York: AL Burt; 2009.
37.
PierceRJ, WorsnopCJ. Upper airway function and dysfunction in respiration. Clin Exp Pharmacol Physiol, 1999; 26(1):1-10.
BrancatisanoT, CollettPW, EngelLA. Respiratory movements of the vocal cords. J Appl Physiol Respir Environ Exerc Physiol, 1983; 54(5):1269-1276.
42.
EnglandSJ, BartlettDJr, DaubenspeckJA. Influence of human vocal cord movements on airflow and resistance during eupnea. J Appl Physiol Respir Environ Exerc Physiol, 1982; 52(3):773-779.
43.
KunaST, VanoyeCR. Laryngeal response during forced vital capacity maneuvers in normal adult humans. Am J Respir Crit Care Med, 1994; 150(3):729-734.
44.
BrancatisanoTP, DoddDS, EngelLA. Respiratory activity of posterior cricoarytenoid muscle and vocal cords in humans. J Appl Physiol Respir Environ Exerc Physiol, 1984; 57(4):1143-1149.
45.
PrudonB, BirringSS, VaraDD, HallAP, ThompsonJP, PavordID. Cough and glottic-stop reflex sensitivity in health and disease. Chest, 2005; 127(2):550-557.
46.
BhabuP, PolettoC, MannE, BielamowiczS, LudlowCL. Thyroarytenoid muscle responses to air pressure stimulation of the laryngeal mucosa in humans. Ann Otol Rhinol Laryngol, 2003; 112(10):834-840.
47.
TheurerJA, BihariF, BarrAM, MartinRE. Oropharyngeal stimulation with air-pulse trains increases swallowing frequency in healthy adults. Dysphagia, 2005; 20(4):254-260.
48.
LeithDE. The development of cough. Am Rev Respir Dis, 1985; 131(5):S39-42.
49.
McCoolFD, LeithDE. Pathophysiology of cough. Clin Chest Med, 1987; 8(2):189-195.
50.
ChatwinM. Mechanical aids for secretion clearance. Int J Respir Care, 2009; 5(2):50-53.
51.
FeinsteinAJ, ZhangZ, ChhetriDK, LongJ. Measurement of cough aerodynamics in healthy adults. Ann Otol Rhinol Laryngol, 2017; 126(5):396-400.
52.
Hoffman RuddyB, Nadun KuruppumullageD, CarnabyG, CraryM, LehmanJ, IlegbusiOJ. Computational modelling of cough function and airway penetrant behavior in patients with disorders of laryngeal function. Laryngoscope Investig Otolaryngol, 2017; 2(1):23-29.
53.
BachJR, SaporitoLR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure: a different approach to weaning. Chest, 1996; 110(6):1566-1571.
54.
SanchoJ, ServeraE, BañulsP, MarínJ. Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener, 2017; 18(7-8):498-504.
55.
ChatwinM, ToussaintM, GonçalvesMR, SheersN, MelliesU, Gonzales-BermejoJ, et al. Airway clearance techniques in neuromuscular disorders: a state of the art review. Respir Med, 2018; 136:98-110.
56.
LacombeM, Del Amo CastrilloL, BoréA, ChapeauD, HorvatE, VaugierI, et al. Comparison of three cough-augmentation techniques in neuromuscular patients: mechanical insufflation combined with manually assisted cough, insufflation-exsufflation alone and insufflation-exsufflation combined with manually assisted cough. Respiration, 2014; 88(3):215-222.
57.
BransonRD, BendittJO. Optimizing mechanical insufflation-exsufflation - much more than cough peak flow. Respir Care, 2020; 65(2):265-268.
58.
BarachAL, BeckG, SmithW. Mechanical production of expiratory flow rates surpassing the capacity of human coughing. Trans Assoc Am Physicians, 1953; 66:315-324.
59.
ShinnJR, KimuraKS, CampbellBR, SunLA, WoottenCT, GarrettCG, et al. Incidence and outcomes of acute laryngeal injury after prolonged mechanical ventilation. Crit Care Med, 2019; 47(12):1699-1706.
60.
WoodsonG. Management of neurologic disorders of the larynx. Ann Otol Rhinol Laryngol, 2008; 117(5):317-326.
61.
García-PachónE, MartíJ, MayosM, CasanP, SanchisJ. Clinical significance of upper airway dysfunction in motor neurone disease. Thorax, 1994; 49(9):896-900.
62.
TomikJ, TomikB, PartykaD, SkladzienJ, SzczudlikA. Profile of laryngological abnormalities in patients with amyotrophic lateral sclerosis. J Laryngol Otol, 2007; 121(11):1064-1069.
63.
HillelA, DrayT, MillerR, YorkstonK, KonikowN, StrandeE, et al. Presentation of ALS to the otolaryngologist/head and neck surgeon: getting to the neurologist. Neurology, 1999; 53(8 Suppl 5):S22-25.discussion S35-26.
64.
RothCR, GlazeLE, GodingGSJr, DavidWS. Spasmodic dysphonia symptoms as initial presentation of amyotrophic lateral sclerosis. J Voice, 1996; 10(4):362-367.
65.
YiuY, CurtisJA, PerrySE, TrocheMS. Relationship of vocal fold atrophy to swallowing safety and cough function in Parkinson's disease. Laryngoscope, 2020; 130(2):303-308.
66.
van den Engel-HoekL, ErasmusCE, van HulstKC, ArvedsonJC, de GrootIJ, de SwartBJ. Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study. J Child Neurol, 2014; 29(5):646-653.
67.
BoelL, PernetK, ToussaintM, IdesK, LeemansG, HaanJ, et al. Respiratory morbidity in children with cerebral palsy: an overview. Dev Med Child Neurol, 2019; 61(6):646-653.
68.
Tabor-GrayLC, GallestaguiA, VasilopoulosT, PlowmanEK. Characteristics of impaired voluntary cough function in individuals with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener, 2019; 20(1-2):37-42.
69.
KunaST, McCarthyMP, SmickleyJS. Laryngeal response to passively induced hypocapnia during NREM sleep in normal adult humans. J Appl Physiol (1985), 1993; 75(3):1088-1096.
70.
DelgusteP, Aubert-TulkensG, RodensteinDO. Upper airway obstruction during nasal intermittent positive-pressure hyperventilation in sleep. Lancet, 1991; 338(8778):1295-1297.
71.
JounieauxV, AubertG, DuryM, DelgusteP, RodensteinDO. Effects of nasal positive-pressure hyperventilation on the glottis in normal sleeping subjects. J Appl Physiol (1985), 1995; 79(1):186-193.
72.
JounieauxV, AubertG, DuryM, DelgusteP, RodensteinDO. Effects of nasal positive-pressure hyperventilation on the glottis in normal awake subjects. J Appl Physiol (1985), 1995; 79(1):176-185.
73.
GeorgesM, AttaliV, GolmardJL, Morélot-PanziniC, Crevier-BuchmanL, ColletJM, et al. Reduced survival in patients with ALS with upper airway obstructive events on non-invasive ventilation. J Neurol Neurosurg Psychiatry, 2016; 87(10):1045-1050.
74.
Sayas CatalánJ, Jiménez HuertaI, Benavides MañasP, LujánM, López-PadillaD, Arias AriasE, et al. Videolaryngoscopy with noninvasive ventilation in subjects with upper-airway obstruction. Respir Care, 2017; 62(2):222-230.
75.
ParreiraVF, JounieauxV, AubertG, DuryM, DelgustePE, RodensteinDO. Nasal two-level positive-pressure ventilation in normal subjects: effects of the glottis and ventilation. Am J Respir Crit Care Med, 1996; 153(5):1616-1623.
76.
Moreau-BussièreF, SamsonN, St-HilaireM, ReixP, LafondJR, NsegbeE, et al. Laryngeal response to nasal ventilation in nonsedated newborn lambs. J Appl Physiol (1985), 2007; 102(6):2149-2157.
77.
OppersmaE, DoorduinJ, GooskensPJ, RoesthuisLH, van der HeijdenE, van der HoevenJG, et al. Glottic patency during noninvasive ventilation in patients with chronic obstructive pulmonary disease. Respir Physiol Neurobiol, 2019; 259:53-57.
78.
AndersenT, SandnesA, HillandM, HalvorsenT, FondenesO, HeimdalJH, et al. Laryngeal response patterns to mechanical insufflation-exsufflation in healthy subjects. Am J Phys Med Rehabil, 2013; 92(10):920-929.
79.
LacombeM, BoréA, Amo CastrilloLD, BoussaïdG, FalaizeL, VlachosE, et al. Peak cough flow fails to detect upper airway collapse during negative pressure titration for cough-assist. Arch Phys Med Rehabil, 2019; 100(12):2346-2353.
80.
AndersenT, HovB, FondenesO, ClemmH, HalvorsenT, Drange RøksundO, et al. Laryngeal responses and airflow geometry in ALS during mechanically assisted cough. Eur Resp J, 2020; 56(Suppl 64):1271.
81.
VollsæterM, SkjoldmoA, RøksundOD, HillandM, AndersenT. Tailoring NIV by dynamic laryngoscopy in a child with spinal muscular atrophy type I. Clin Case Rep, 2021. doi: 10.1002/ccr3.3905.
82.
PazC, SuárezE, PargaO, VenceJ. Glottis effects on the cough clearance process simulated with a CFD dynamic mesh and Eulerian wall film model. Comput Methods Biomech Biomed Engin, 2017; 20(12):1326-1338.
83.
LachalR, LouisB, SubtilF, GuérinC. Bench assessment of the effect of a collapsible tube on the efficiency of a mechanical insufflation-exsufflation device. Respir Care, 2019; 64(7):752-759.
84.
CondeB, MartinsN, BrandãoM, PimentaAC, WinckJC. Upper airway video endoscopy: assessment of the response to positive pressure ventilation and mechanical in-exsufflation. Pulmonology, 2019; 25(5):299-304.
85.
AtkesonAD, RoyChoudhuryA, Harrington-MoroneyG, ShahB, MitsumotoH, BasnerRC. Patient-ventilator asynchrony with nocturnal noninvasive ventilation in ALS. Neurology, 2011; 77(6):549-555.
86.
BlochKE. Polysomnography: a systematic review. Technol Health Care, 1997; 5(4):285-305.
87.
HovB, AndersenT, ToussaintM, FondenesO, CarlsenKCL, HovlandV. Optimizing expiratory flows during mechanical cough in a pediatric neuromuscular lung model. Pediatr Pulmonol, 2020; 55(2):433-440.
88.
TuJ, InthavongK, AhmadiG. Computational fluid and particle dynamics in the human respiratory system. Netherlands: Springer; 2013.
89.
RuoppoloG, OnestiE, GoriMC, SchettinoI, FrascaV, BiasiottaA, et al. Laryngeal sensitivity in patients with amyotrophic lateral sclerosis. Front Neurol, 2016; 7:212.
90.
KoufmanJA, BlockC. Differential diagnosis of paradoxical vocal fold movement. Am J Speech Lang Pathol, 2008; 17(4):327-334.
91.
MaschkaDA, BaumanNM, McCrayPBJr, HoffmanHT, KarnellMP, SmithRJ. A classification scheme for paradoxical vocal cord motion. Laryngoscope, 1997; 107(11 Pt 1):1429-1435.
92.
KühnleinP, GdyniaHJ, SperfeldAD, Lindner-PflegharB, LudolphAC, ProsiegelM, et al. Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis. Nat Clin Pract Neurol, 2008; 4(7):366-374.
93.
ErtekinC, AydogduI, YüceyarN, KiyliogluN, TarlaciS, UludagB. Pathophysiological mechanisms of oropharyngeal dysphagia in amyotrophic lateral sclerosis. Brain, 2000; 123(1):125-140.
94.
LangmoreSE, SchatzK, OlsonN. Endoscopic and videofluoroscopic evaluations of swallowing and aspiration. Ann Otol Rhinol Laryngol, 1991; 100(8):678-681.
95.
SandnesA, AndersenT, HillandM, EllingsenTA, HalvorsenT, HeimdalJH, et al. Laryngeal movements during inspiratory muscle training in healthy subjects. J Voice, 2013; 27(4):448-453.
96.
HeimdalJH, RoksundOD, HalvorsenT, SkadbergBT, OlofssonJ. Continuous laryngoscopy exercise test: a method for visualizing laryngeal dysfunction during exercise. Laryngoscope, 2006; 116(1):52-57.
97.
WalstedES, SwantonLL, van van SomerenK, MorrisTE, FurberM, BackerV, et al. Laryngoscopy during swimming: a novel diagnostic technique to characterize swimming-induced laryngeal obstruction. Laryngoscope, 2017; 127(10):2298-2301.
98.
KamityR, FerraraL, DumpaV, ReynoldsJ, IslamS, HannaN. Simultaneous videofluoroscopy and endoscopy for dysphagia evaluation in preterm infants: a pilot study. Front Pediatr, 2020; 8:537.
99.
MarraraJL, DucaAP, DantasRO, TrawitzkiLV, LimaRA, PereiraJC. Swallowing in children with neurologic disorders: clinical and videofluoroscopic evaluations. Pro Fono, 2008; 20(4):231-236.
100.
FukuharaT, DonishiR, MatsudaE, KoyamaS, FujiwaraK, TakeuchiH. A novel lateral approach to the assessment of vocal cord movement by ultrasonography. World J Surg, 2018; 42(1):130-136.
101.
SimondsAK. Progress in respiratory management of bulbar complications of motor neuron disease/amyotrophic lateral sclerosis?. Thorax, 2017; 72(3):199-201.
102.
Gómez-MerinoE, SanchoJ, MarínJ, ServeraE, BlascoML, BeldaFJ, et al. Mechanical insufflation-exsufflation: pressure, volume, and flow relationships and the adequacy of the manufacturer's guidelines. Am J Phys Med Rehabil, 2002; 81(8):579-583.
103.
AndersenTM, SandnesA, FondenesO, ClemmH, HalvorsenT, NilsenRM, et al. Laryngoscopy can be a valuable tool for unexpected therapeutic response in noninvasive respiratory interventions. Respir Care, 2018; 63(11):1459-1461.
104.
VolpeMS, NavesJM, RibeiroGG, RuasG, AmatoMBP. Airway clearance with an optimized mechanical insufflation-exsufflation maneuver. Respir Care, 2018; 63(10):1214-1222.
105.
VolpeMS, GuimarãesFS, MoraisCC. Airway clearance techniques for mechanically ventilated patients: insights for optimization. Respir Care, 2020; 65(8):1174-1188.
106.
HarrisRS, LawsonTV. The relative mechanical effectiveness and efficiency of successive voluntary coughs in healthy young adults. Clin Sci, 1968; 34(3):569-577.
