Researchers have identified the processes that cause wheezing in the lungs

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A team of engineers has identified the ‘violent’ physical processes at work inside the lungs which cause wheezing, a condition which affects up to a quarter of the world’s population.

The researchers, from the University of Cambridge, used modelling and high-speed video techniques to show what causes wheezing and how to predict it. Their results could be used as the basis of a cheaper and faster diagnostic for lung disease that requires just a stethoscope and a microphone.

Improved understanding of the physical mechanism responsible for generating wheezing sounds could provide a better causal link between symptoms and disease, and help improve diagnosis and treatment. The results are reported in the journal Royal Society Open Science.

At some point, most of us have experienced wheezing, a high-pitched whistling sound made while breathing. For most people, the phenomenon is temporary and usually the result a cold or mild allergic reaction.

However, regular or chronic wheezing is often a symptom of more serious conditions, such as asthma, emphysema, chronic obstructive pulmonary disease (COPD) or certain cancers.

“Because wheezing makes it harder to breathe, it puts an enormous amount of pressure on the lungs,” said first author Dr. Alastair Gregory from Cambridge’s Department of Engineering.

“The sounds associated with wheezing have been used to make diagnoses for centuries, but the physical mechanisms responsible for the onset of wheezing are poorly understood, and there is no model for predicting when wheezing will occur.”

Co-author Dr. Anurag Agarwal, Head of the Acoustics lab in the Department of Engineering, said he first got the idea to study wheezing after a family vacation several years ago.

“I started wheezing the first night we were there, which had never happened to me before,” he said. “And as an engineer who studies acoustics, my first thought was how cool it was that my body was making these noises. After a few days however, I was having real trouble breathing, which made the novelty wear off pretty quickly.”

Agarwal’s wheezing was likely caused by a dust mite allergy, which was easily treated with over-the-counter antihistamines. However, after speaking with a neighbour who is also a specialist in respiratory medicine, he learned that even though it is a common occurrence, the physical mechanisms that cause wheezing are somewhat mysterious.

“Since wheezing is associated with so many conditions, it is difficult to be sure of what is wrong with a patient just based on the wheeze, so we’re working on understanding how wheezing sounds are produced so that diagnoses can be more specific,” said Agarwal.

The airways of the lung are a branching network of flexible tubes, called bronchioles, that gradually get shorter and narrower as they get deeper into the lung.

In order to mimic this setup in the lab, the researchers modified a piece of equipment called a Starling resistor, in which airflow is driven through thin elastic tubes of various lengths and thicknesses.

Co-author and computer vision specialist Professor Joan Lasenby developed a multi-camera stereoscopy technique to film the air being forced through the tubes at different degrees of tension, in order to observe the physical mechanisms that cause wheezing.

“It surprised us just how violent the mechanism of wheezing is,” said Gregory, who is also a Junior Research Fellow at Magdalene College.

We found that there are two conditions for wheezing to occur: the first is that the pressure on the tubes is such that one or more of the bronchioles nearly collapses, and the second is that air is forced though the collapsed airway with enough force to drive oscillations.”

Once these conditions are met, the oscillations grow and are sustained by a flutter mechanism in which waves travelling from front to back have the same frequency as the opening and closing of the tube. “A similar phenomenon has been seen in aircraft wings when they fail, or in bridges when they collapse,” said Agarwal.

“When up and down vibrations are at the same frequency as clockwise and anticlockwise twisting vibrations, we get flutter that causes the structure to collapse. The same process is at work inside the respiratory system.”

Using these observations, the researchers developed a ‘tube law’ in order to predict when this potentially damaging oscillation might occur, depending on the tube’s material properties, geometry and the amount of tension.

“We then use this law to build a model that can predict the onset of wheezing and could even be the basis of a cheaper and faster diagnostic for lung disease,” said Gregory. “Instead of expensive and time-consuming methods such as X-rays or MRI, we wouldn’t need anything more than a microphone and a stethoscope.”

A diagnostic based on this method would work by using a microphone – early tests were done using the in-built microphone on a normal smartphone – to record the frequency of the wheezing sound and use this to identify which bronchiole is near collapse, and whether the airways are unusually stiff or flexible in order to target treatment.

The researchers hope that by finding changes in material properties from wheezing, and locations that wheezes come from, the additional information will make it easier to distinguish between different conditions, although further work in this area is still needed.


Wheezing is the symptomatic manifestation of any disease process that causes airway obstruction. Rene Laennec’s development of the stethoscope in 1816 has enabled a better appreciation of wheeze at the bedside; in comparison to the previously established practice of ear-to-chest auscultation.

Wheeze is a musical, high-pitched, adventitious sound generated anywhere from the larynx to the distal bronchioles during either expiration or inspiration. Modern-day, computerized, waveform analysis has allowed us to characterize wheeze with more precision and given us its definition as a sinusoidal waveform, typically between 100 Hz and 5000 Hz with a dominant frequency of at least 400 Hz, lasting at least 80 milliseconds. Wheeze may be audible without the aid of a stereoscope when the sound is loud, but in most cases, wheezes are auscultated with a stethoscope.

The presence of wheezing does not always mean that the patient has asthma, and a proper history and physical exam are required to make the diagnosis.[1][2][3][4]

Etiology
Wheezing is commonly experienced by people who have asthma; although, it can be heard in people with foreign bodies, congestive heart failure, a malignancy of the airway, or any lesion that causes narrowing of the airways. The presence of wheezing during expiration indicates that the individual’s peak expiratory flow rate is less than fifty percent compared to normal. The quality and duration of wheezing also depend on where in the airways the obstruction is located.

In asthma, the wheezing is due to narrowing of the lower airways whereas with malignancies the obstruction is usually in the upper, more proximal airways.

In rare cases, wheezing may be heard both during inspiration and expiration. In severe asthma, in fact, no wheeze may be heard as the air flow will be so severely reduced and chest auscultation will be silent. Since any process that reduces airway caliber generates wheeze, below are some of the many of the conditions that can cause wheeze:

Respiratory infections (croup, laryngitis)
Obstructive airway diseases (asthma,
chronic obstructive pulmonary disease [COPD], anaphylaxis, bronchiolitis)
Pulmonary peribronchial edema (congestive heart failure)
Vocal cord dysfunction (paradoxical vocal fold motion [PVFM], vocal cord paralysis)
Post nasal drip
Airway compression: Intrinsic or extrinsic (squamous cell carcinomas, goiter)
Hyperdynamic airway collapse (tracheobronchomalacia)
Carcinoid tumors
Foreign body inhalation
Forced exhalation by normal individuals[5][6][7]

Epidemiology
The reported prevalence of wheezing amongst young children between 2 to 3 years of age is reported around 26% in the United States. The global prevalence is lower in the adolescent age range approximately 12%. Global surveys reveal a similar prevalence in adults, with European and Australian surveys reporting the highest prevalence rates, up to 17%.[8]

Pathophysiology
Wheezes are thought to be the product of fluttering vibrations of narrowed airway walls, induced by a diminished air flow velocity. The characteristics of their sound include how loud they are (i.e., the amplitude), how long they last and how intense (i.e., high pitched) they sound.

A physiologic trial done in the 1980s identified the determinants of the pitch of a sound that is generated within collapsible tubes. It was determined that the pitch of a wheeze is a reflection of the stiffness, the thickness and longitudinal tension of the airway’s wall also.

Subsequent clinical studies have shown that the pitch and more so duration of wheeze are the only two characteristics that correlate well with the severity of airway obstruction. The degree of bronchial obstruction is also proportional to the number of airways that are producing wheeze.

And so, the amplitude of auscultated wheeze has no bearing on the severity of airway obstruction. At the very severe end of airway obstruction, if there is very little to no air flow, then no wheeze will be heard despite severe airway obstruction.[9][10][11][12]

History and Physical
History should be targetted toward the various etiologies of wheezing listed above. For example, patients who have had head and neck cancer surgery and/or radiation may develop vocal cord paralysis. Additionally, a prior history of endotracheal intubation can alert one to the possibility of tracheal, subglottic stenosis.

Physical examination of the trachea and thorax will identify wheeze. Wheeze associated with asthma is most commonly heard during expiration; however, wheeze is neither sensitive or specific for asthma, so the wheezes can certainly extend into inspiration also. Upper airway obstruction from tonsilar hypertrophy can be evaluated with an oral examination and palpation of the neck could identify a goiter.[13]

Evaluation
When wheezing is heard, some work up is required because it is an abnormal sound. The first imaging test of choice in a patient with wheezing is a chest x-ray to look for a foreign body or a lesion in the central airway. In the non-acute setting, if asthma is suspected, the next step is to obtain baseline pulmonary function tests with bronchodilator administration.

Following this, it may be necessary perform an airway challenge test with a bronchoconstrictive agent such as methacholine. If the wheezing resolves with a bronchodilation agent, a tumor or mass as the cause is a much less likely consideration. If there is no resolution after a breathing treatment, and a tumor or mass is suspected, then a CT scan of the chest and bronchoscopy may be required if possible malignancy is suspected on CT.[7]

Treatment / Management
Treatment predominantly revolves around the suspected etiology of the wheezing. The ubiquitous approach to ensuring Airway, Breathing, and Circulation (ABCs) are stable is the priority. Those with signs of impending respiratory failure may require either noninvasive positive pressure ventilation or invasive mechanical ventilation following endotracheal intubation.

In cases of anaphylaxis, epinephrine would be required. Nebulized, short-acting, b2 agonist such as albuterol and nebulized short-acting muscarinic antagonists are often administered while further workup is being performed.[7]

Differential Diagnosis
Other lung sounds that can be mistaken for or that overlap with wheezes are rhonchi and stridor. Rhonchi share similar characteristics to wheezes, with the main difference being a lower dominant frequency of fewer than 200 MHz. This lower frequency is described as a snoring-like sound.

Stridor is a higher-pitched and higher amplitude sound that is due to turbulent airflow around a region of upper airway obstruction. It is typically an inspiratory sound that is far more pronounced when auscultated over the trachea than the thorax.[14]

Possible causes of wheezing include:

Allergies
Anaphylaxis
Asthma
Bronchiectasis
Bronchiolitis
Bronchitis
Chronic Obstructive Pulmonary Disease (COPD)
Emphysema
Epiglottitis
Foreign object
Gastroesophageal reflux disease (GERD)
Heart failure
Lung cancer
Drugs (i.e. aspirin)
Obstructive sleep apnea
Pneumonia
Respiratory syncytial virus (RSV)
Respiratory tract infection
Smoking
Vocal cord dysfunction

Enhancing Healthcare Team Outcomes
Wheezing is a common sign encountered in clinical practice by the nurse practitioner, primary care provider, internist, cardiologist, and the pulmonologist. When wheezing is heard, some workup is required because it is an abnormal sound. The first imaging test of choice in a patient with wheezing is a chest x-ray to look for a foreign body or a lesion in the central airway.

In the non-acute setting, if asthma is suspected, the next step is to obtain baseline pulmonary function tests with bronchodilator administration. Following this, it may be necessary to perform an airway challenge test with a bronchoconstrictive agent such as methacholine. If the wheezing resolves with a bronchodilation agent, a tumor or mass as the cause is a much less likely consideration. If there is no resolution after a breathing treatment, and a tumor or mass is suspected, then a CT scan of the chest and bronchoscopy may be required if possible malignancy is suspected on CT.

reference link: https://www.ncbi.nlm.nih.gov/books/NBK482454/


More information: An Experimental Investigation to Model Wheezing in Lungs, Royal Society Open Scienceroyalsocietypublishing.org/doi/10.1098/rsos.201951 

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