Acta Biomed 2018; Vol. 89, N. 4: 477-480 DOI: 10.23750/abm.v89i4.

6182 © Mattioli 1885

Focus on

Cough, a vital reflex. Mechanisms, determinants and

measurements
Francesco Andrani, Marina Aiello, Giuseppina Bertorelli, Ernesto Crisafulli, Alfredo Chetta
Department of Medicine and Surgery, Unit of Respiratory Diseases, University of Parma, Parma Italy

Summary. Cough is a natural defense mechanism that protects the respiratory tract from inhaling foreign
bodies and by clearing excessive bronchial secretions. As a spontaneous reflex arc, it involves receptors, an af-
ferent pathway, a center processing information, an efferent pathway and effectors. The determinant factor of
cough efficacy is the operational volume of the lung, which in turn relies on the strength and coordination of
respiratory and laryngeal muscles as well as on lung mechanics. Respiratory muscle weakness and dysfunction
as well as expiratory flow limitation and lung hyperinflation may occur in some neuromuscular disorders and
in obstructive airway diseases, respectively. Accordingly, all these diseases may show an ineffective cough. In
this brief overview, we deal with the determinants of the cough efficacy and the clinical conditions affecting
cough efficacy as well as the cough’s efficacy measurements in clinical setting. (www.actabiomedica.it)

Key words: cough, cough peak flow, neuromuscular disorders, chronic obstructive pulmonary disease

Cough is a natural defense mechanism that along 1. Receptorial phase: there is the stimulation of
with mucociliary clearance, bronchoconstriction and cough receptors that are activated and, accord-
phagocytosis can effectively protect the respiratory ingly, send an impulse to the center through the
tract from inhaling foreign bodies and by clearing ex- vagus nerve;
cessive bronchial secretions (1). 2. Inspiratory phase: that consists in a wide open-
Cough may be a voluntary act or a spontaneous ing of the glottis by contraction of the arytenoid
reflex arc and in this case involves receptors, an affer- cartilage with rapid inhalation, which involves
ent pathway, a center processing information, an ef- an average of 50% of vital capacity with wide
ferent pathway and effectors. The receptors are placed variations in relation to the stimulus and the
throughout the bronchial tree and, although in a lesser type of receptors;
extent, also in other areas: ear, paranasal sinuses, pleu- 3. Compressive phase: that consists in a prompt clo-
ra, diaphragm, pericardium and esophagus. From re- sure of the glottis following the contraction of
ceptors the afferent impulses are channeled through the adductor muscles of the arytenoid cartilages
the vagus nerve in the medulla oblongata, where they with consequent adduction of the vocal cords.
are processed. Then, efferent impulses are conveyed by At the same time, there is a strong contraction
motor nerves and reach the effectors, which are the of the abdominal muscles and other expiratory
respiratory and laryngeal muscles. muscles resulting in an increased intrapulmo-
Schematically, we may distinguish four different nary pressure and compression of the alveoli
phases of cough, as a vital reflex arc, the first of which and bronchioles.
is a part in the afferent pathway while the last three in 4. Expiratory phase: in this final phase, vocal cords
the efferent one (2): and epiglottis open suddenly for action of the
478 F. Andrani, M. Aiello, G. Bertorelli, et al.

abductor muscle of the arytenoid cartilages, terms of strength or coordination, can significantly
thereby causing the explosive leakage of air limit the development of compression phase and the
from the lungs to the outside. Subsequently, the following increase in intrapulmonary pressure.
exhalation continues, favored by the complete The decrease of operational volume of the lung
relaxation of the diaphragm. can be the consequence not only of a weakness of res-
In this brief overview, we deal with the determi- piratory muscles, but also of the expiratory flow limita-
nants of the cough efficacy and the clinical conditions tion and lung hyperinflation. These pathophysiological
affecting cough efficacy as well as the cough’s efficacy features may occur in some obstructive airway dis-
measurements in clinical setting. eases, such as chronic obstructive pulmonary disease
(COPD), cystic fibrosis, bronchiectasis, tracheomala-
cia and asthma. Accordingly, all these diseases may be
Determinants of cough efficacy associated with cough inefficacy (1). Expiratory flow
limitation and lung hyperinflation may result from dif-
Since the result of the cough reflex arc is the pro- ferent mechanisms, such as bronchoconstriction and/
duction of an airflow, the determinant factor of cough or an impairment of elastic recoil of the lung.
efficacy is the operational volume of the lung (3),
which in turn relies on the strength and coordination
of respiratory and laryngeal muscles as well as on lung Measurements of cough efficacy
mechanics.
The weakness and/or the incoordination of the Cough efficacy can be measured by means of the
respiratory and/or laryngeal muscles may significantly gastric pressure (Pga), as well as the peak flow (CPF)
decrease the driving pressure applied to the alveoli and and exhaled volume (CEV) at the mouth during a vol-
to the bronchial airways. The reduction in driving pres- untary and maximal cough (4) (Figure 1).
sure consequently results in low expiratory volumes Pga is measured using a commercially available la-
and flows during cough. A weakness or a dysfunction tex balloon catheter, which is inserted through the nose
of the respiratory muscles are common conditions in and positioned in the stomach. The balloon catheter
many neuromuscular disorders (Table 1). At the same is connected to a manometer and the subject is asked
time the impairment of laryngeal muscles, either in to perform 3-6 coughs, starting from maximal inspira-
tion. In normal subjects, Pga values are greater than
or equal to 100 cmH2O in women and 130 in men
Tabella 1. Neuromuscolar desease with respiratory muscle
weakness cmH2O (5). The measurement of Pga is an invasive test,
which on the other hand enables to directly measure
Diseases of the Central • Parkinson’s disease
Nervous System • Quadriplegia the driving pressure, developed by the synergistic con-
• Multiple sclerosis traction of the abdominal muscles during cough.
• Poliomyelitis The CPF is assessed while the subject coughs in a
• Motor neuron disease tightly fitting full-face mask, adherent to patient’s face
Peripheral neuropathies • Guillain-Barré syndrome
and connected to a computerized pneumotachograph,
• Charcot-Marie-Tooth disease starting from maximal inspiration. The test is repeated
3-6 times. Healthy individuals of both sexes develop
Myasthenia • Myasthenia gravis CPF values greater than or equal to 360 L/min (4).
• Lambert-Eaton syndrome
Patients with values of CPF under 160 L/min have a
Muscular dystrophies • Duchenne dystrophy quite ineffective cough and require manually assisted
• Myotonic dystrophy cough and/or mechanical insufflation-exsufflation (4).
CEV can be measured together with CPF assess-
Toxic myopathies • Alcoholic myopathy ment. In healthy individuals, CEV values are usually
• Steroid myopathy
greater than 1 L with an average value of 2.4 L (6).
Cough, a vital reflex 479

a) b)

Figure 1. Simultaneous recordings of gastric pressure (Pga) ex-

c) piratory volume (CEV) and expiratory flow rate (CPF) during
coughs in a healthy subject (1a), a patient with amyotrophic
lateral sclerosis (1b) and a patient with COPD (1c)

tion pneumonia. Up to now, no data has been published

on the clinical relevance of the CEV measurement.
The measurement of cough efficacy should be a
routine assessment in patients suffering from progres-
sive neurological disorders with lung involvement and
in patients who are at high risk of an ineffective cough.
In these patients, a non-invasive evaluation of respira-
tory muscles function is required and usually consists
in some volitional tests. These tests include the vital
capacity (CV) measured both in orthostatic and supine
position, the maximum inspiratory (MIP) and expira-
CPF evaluation is clinically relevant and it can be tory (MEP) mouth pressures, the nasal pressure during
considered an overall parameter of cough efficacy (7). a sharp, maximal and short (less than 0.5 seconds) sniff
Neuromuscular patients with values of CPF less than maneuver, which is a complementary test to MIP (4).
270 L/minute are at risk of retention of bronchial secre- The mouth pressure during a maximal whistle is a vo-
tions and respiratory failure in case of bronchial infec- litional, non-invasive test, which may be considered as
tion (8). Interestingly, as shown in a study in patients a complementary test to MEP (12) and is particularly
with Multiple Sclerosis (9), the cough efficacy as meas- useful in children having difficulties to perform MEP
ured by CPF significantly correlates with the disability manoeuvre (13). Non-volitional and invasive tests may
status calculated by means of Expanded Disability Sta- be required in non-cooperative patients or in patients
tus Scale (EDSS). In patients with stable amyotrophic providing non-univocal results at volitional tests (4).
lateral sclerosis, CPF <4.25 L/sec could also predict the Moreover, in case of a documented impairment of res-
risk of ineffective spontaneous cough during a respirato- piratory muscle function, an arterial blood-gas analysis
ry tract infection (10). Moreover, a recent study (11) has may be requested to ascertain whether a hypoxemic-
shown that in patients with acute stroke, higher values of hypercapnic respiratory failure due to a ventilatory
CPF are associated with a low risk of secondary aspira- pump impairment may occur.
480 F. Andrani, M. Aiello, G. Bertorelli, et al.

Patients with a decreased operational volume of 3. Smith JA, Aliverti A, Quaranta M, McGuinness K, Kelsall
the lung due to an obstructive ventilatory defect and A, Earis J, Calverley PM. Chest wall dynamics during vol-
untary and induced cough in healthy volunteers. J Physiol
lung hyperinflation show a reduced forced expiratory 2012; 590: 563-74.
volume at 1st second (FEV1)/CV ratio and an increase 4. Chetta A, Aiello M, Tzani P, Olivieri D. Assessment and
in the Residual Volume (RV)/Total Lung Capacity monitoring of ventilatory function and cough efficacy in
(TLC) ratio. In these patients, the CPF and CEV re- patients with amyotrophic lateral sclerosis. Monaldi Arch
Chest Dis. 2007 Mar; 67(1): 43-52.
duction may also occur without a reduction of the Pga, as
5. Man W D-C Man WD, Kyroussis D, Fleming TA, Chetta
a consequence of a normal driving pressure (Figure 1c). A, Harraf F, Mustfa N, Rafferty GF, Polkey MI, Moxham J.
Cough Gastric Pressure and Maximum Expiratory Mouth
Conclusions Pressure in Humans. Am J Respir Crit Care Med 2003;
168: 714-7.
6. Sivasosthy P, Brown L, Smith IE, Shneerson JM. Effect
In clinical practice, it is a common experience of manually assisted cough and mechanical insufflation on
that infections of the respiratory tract are the most cough flow of normal subjects, patients with chronic ob-
frequent causes of morbidity and mortality in patients structive pulmonary disease (COPD), and patients with res-
with neuromuscular diseases, as well as in patients with piratory muscle weakness. Thorax 2001; 56: 438-44.
7. Tzani P, Chiesa S, Aiello M, Scarascia A, Catellani C, Elia
broncho-obstructive diseases.
D, Marangio E, Chetta A. The value of cough peak flow in
Cough is a reflex arc, which acts as a defensive the assessment of cough efficacy in neuromuscolar patients.
physiological mechanism against the inhalation of for- A cross sectional study. Eur J Phys Rehabil Med 2014; 50:
eign bodies and the pathogens of the respiratory tract. 427-32.
8. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary
In order to produce an effective cough, an operational
morbidity for patients with Duchenne Muscular Dystrophy.
volume of the lung should be in the normal range and Chest 1997; 112: 1024-28.
this fact involves a normal function of the respiratory 9. Aiello M, Rampello A, Granella F, Maestrelli M, Tzani P,
and glottis muscles as well as requires normal lung me- Immovilli P, Franceschini M, Olivieri D, Chetta A. Cough
chanics. efficacy is related to the disability status in patients with
multiple sclerosis. Respiration 2008;76: 311-6.
In order to improve cough efficacy in neuro- 10. Sancho J, Servera E, Díaz J, Marín J. Predictors of ineffec-
muscular patients, devices capable of assisting both the tive cough during a chest infection in patients with stable
inspiratory and the expiratory phase of cough and of amyotrophic lateral sclerosis. Am J Respir Crit Care Med
improving the operational volume of the lung are now 2007; 175: 1266-71.
11. Kulnik ST, Birring SS, Hodsoll J, Moxham J, Rafferty GF,
available. Notably, in bulbar and in non-bulbar ALS pa-
Kalra L. Higher cough flow is associated with lower risk of
tients, mechanical insufflation-exsufflation can signifi- pneumonia in acute stroke. Thorax 2016; 71: 474-5.
cantly increase air flow during cough (14). Moreover, in 12. Chetta A, Harris ML, Lyall RA, Rafferty GF, Polkey MI,
patients with COPD the use of bronchodilators, such Olivieri D, Moxham J. Whistle mouth pressure as test of
as beta2-agonists or muscarinic antagonists, can signifi- expiratory muscle strength. Eur Respir J 2001; 17: 688-95.
13. Aloui S, Khirani S, Ramirez A, Colella M, Louis B, Amad-
cantly reduce the exacerbation rate and this effect might deo A, Fauroux B. Whistle and cough pressures in children
be linked to an improvement in operational volume of with neuromuscular disorders. Respir Med. 2016; 113: 28-36
the lung and, accordingly, to a more effective cough. 14. Mustfa N, Aiello M, Lyall RA, Nikoletou D, Olivieri D,
Leigh PN, Davidson AC, Polkey MI, Moxham J. Cough
augmentation in amyotrophic lateral sclerosis. Neurology
References 2003; 61: 1285-7.

1. Bouros D, Siafakas N, Green M. Cough. Physiological and

Pathophysiological Considerations. In: C. Roussos (Ed). The Received: 10 February 2017
Thorax, NY Marcel Dekker 1995. Part B: Applied Physiol- Accepted: 11 February 2017
ogy, second edition. New York: Marcel Dekker Inc., 1995: Correspondence:
1346-54. Dr Francesco Andrani
2. Yanagihara N, Von Leden H, Werner-Kukuk E. The physi- UOC Clinica Pneumologica
cal parameters of cough: the larynx in a normal single cough. Padiglione Rasori, AOU Parma
Acta Otolaryngol 1966; 61: 495-510. E-mail: andrani.francesco@libero.it