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Allergies, Asthma, Exercise, Hyperventilation, and Panic Disorders;
is there a common link?

Article written: September 2002

The high prevalence of allergic diseases (prevalence of atopy in New Zealand is about 40%) and improved diagnostic techniques and treatment has had a great impact on allergy care to allergic patients.

Allergic reactions can express themselves in many different organs and in any age group.

As an allergist, we get to see a varied group of patients, as the specialty attracts all the "difficult cases" that have been seen by several other specialist. It is not unusual for patient who can’t find an explanation for their symptoms to assume that "it must be an allergy".

Typical allergic symptoms include asthma, rhinoconjunctivitis (hay fever), and eczema, generally referred to as "atopic diseases". Typically, an atopic patient develops a spectrum of "atopic diseases" with age, sometimes referred to as the "atopic march". In infancy, gastrointestinal and eczema, often caused by food allergens, predominate. Asthma and rhinitis to inhalants develop later. In dealing with the atopic individual, it is a lot easier to see the patient as a whole as often the symptoms, varied, as they may seem are often interrelated.

Atopy is inherited. For example, the risk of a child developing an atopic disease (an IgE-mediated allergy) is 40-60% if both parents are atopic. So far no specific genetic marker has been identified because atopy is a polygenic disorder. The new definition of atopy is a familial or personal tendency to develop allergen –specific IgE on exposure to environmental allergens, and to suffer typical allergic symptoms (asthma, eczema and hay fever).

Asthma is a reversible obstructive, inflammatory disorder of the large and small airways in which the degree of obstruction varies spontaneously and in response to therapy. Allergy is an important trigger in about 90% of children and 50% of adults with asthma. Onset can be at any age. Although symptoms tend to be episodic, even in patients with mild asthma, the inflammatory process is chronic.

Clinical features consistent with asthma include episodic or chronic:
Wheezing
Cough
Dyspnea (shortness of breath)
Chest tightness (sometimes described as chest pain, chest congestion, inability to take a deep breath).

Exercise-induced asthma (EIA), also known as exercise-induced bronchospasm describes acute, temporary lung airway narrowing that occurs during and/or after physical activity. The underlying causes of exercise-induced asthma are not clearly understood. Most patients with asthma do have some degree of exercise-induced symptoms. Changes in airway temperature, changes in airway dryness and congestion of the bronchial arteries, which results in bronchial mucosal vascular engorgement, are thought to be possible causes. Currently, the relationship between bronchial blood flow and bronchial heat exchange is thought to influence the development of airway narrowing following over breathing related to exercise.

Depending on the study population, exercise protocol, detection method, and environmental conditions, the prevalence of exercise-induced asthma ranges from 10 to 50 percent. In the general population, an incidence of 10 to 15 percent is a reasonable figure.

Hyperventilation Syndrome

Hyperventilation Syndrome (HVS) represents a relatively common emergency room presentation that some clinicians readily recognize. However, the syndrome has defied precise definition and explanation of the underlying pathophysiology for the past 100 years.

A definition used by Edward Newton, Department of Emergency Medicine, University of South California, Los Angeles, is "HVS is a condition in which minute ventilation exceeds metabolic demands, resulting in haemodynamic and chemical changes that produce characteristic symptoms. Symptoms of HVS and panic disorder overlap considerable, although the 2 conditions remain distinct. Approximately 50% of patients with panic disorder and 60% of patients with agoraphobia manifest hyperventilation as part of their symptomatology, whereas only 25% of patients with HVS manifest panic disorder."

Frequency
In the USA as many as 10% of patients in general internal medicine practice is reported to have HVS as their primary diagnosis.

Symptoms
Patients with acute HVS may present with agitation and anxiety.

Most commonly the history is of sudden onset of chest pain, dyspnea (shortness of breath) or neurological symptoms (e.g., dizziness, weakness, paraesthesia) following a stressful event.

Patients with chronic HVS have recurrent chest pain, dyspnea ort neurological symptoms, but usually with numerous presentations in the past.

Acute Hyperventilation
Agitation, increased respiratory rate, chest pain, dyspnea, wheezing, dizziness, palpitations, tetanic cramps, paresthesia, generalized weakness, and syncope.
Patients often complain of a sense of suffocation.
Often an emotionally stressful event can be identified.

Cardiac symptoms
Chest pain can be confused with angina, and to complicate matters ECG changes are common in patients with HVS.

Central nervous symptoms
CNS symptoms are related to reduced cerebral CO2.
Dizziness, weakness, confusion, and agitation are common.
Rarely, syncope or seizure may be provoked.
Paraesthesia (pins and needles), bilaterally in upper limbs.
Left sided unilateral paraesthesia occurs in 80% of cases.
Perioral numbness is very common.

GI symptoms
Bloating, belching, flatus, epigastric pressure.

Chronic hyperventilation
Diagnosis is usually more difficult than that of acute HVS because the hyperventilation is not clinically apparent.
Frequent sighing respirations, 2-3 per minute.
Chest wall tenderness, numbness, tingling.
Two thirds have a persistently low pCO2, with near normal pH.

A case of Hyperventilation/Panic Disorder masquerading as Idiopathic Anaphylaxis

Introduction
Idiopathic Anaphylaxis (IA) is an immediate generalized allergic reaction in which the acute episode is spontaneous and endogenous (internal) in origin. Anaphylaxis from any cause implies the potential for life-threatening or fatal reactions and such have occurred from IA. The diagnosis of IA may be reached with reasonable certainty by consideration and exclusion of recognized causes of immediate generalized allergic reactions. Thus, the diagnosis of IA becomes a diagnosis of exclusion, but treatment should be started as soon as possible to avoid hospitalization and potential death.

CASE REPORT (1)

CHIEF COMPLAINT
Admitted to hospital overnight while on holiday, for "Idiopathic Anaphylaxis" and discharged with an Epi-pen (Adrenaline auto injection)

HISTORY OF PRESENT ILLNESS
A 50-year-old male developed an episode of itchy ears, eyes, scalp starting at 8pm. 10minutes later he developed tingling of hands and feet assoc with dizziness and "near collapse". Last meal at 1pm. Denies taking any food or medication (specifically enquired about aspirin and NASID). Taken to hosp and observed overnight, given antihistamines only.

PAST MEDICAL HISTORY
He denied a prior history of anaphylaxis, but suffered from mild hay fever

PHYSICAL EXAMINATION
Peak Flow = 500

SKIN PRICK TEST RESULT
House dust mite = 10mm, cat=8 and grass = 6mm, histamine=5mm

Results confirmed his Atopic status.

CLINICAL COURSE
Since this episode the patient has been carrying around an Epi-pen, but has had no further reactions.

DISCUSSION
Suspected anaphylaxis is one of the common referrals seen by allergist. It is often very difficult to differentiate ‘true anaphylaxis’ from panic disorders, because oftentimes the patient will be atopic, and suffer from mild asthma, and gets acute urticaria, which makes the possibility of anaphylaxis likely. Because the Allergist usually sees the patient, sometimes months after the event has taken place, important information might be forgotten or not recorded at the time, and usually there is no physical abnormality to find on examining the patient It is often difficult to make a diagnosis and one has to look for subtle clues like presence of tingling (pins and needles), circumoral numbness.

The differential diagnosis of Anaphylaxis should include (and before the diagnosis of Idiopathic Anaphylaxis is made the following should be excluded):

Foods: peanut, nuts, seafood, egg, milk, wheat
Medication: Penicillins, Aspirin, NSAIDs, ACE inhibitors (antihypertensive)
Food supplements: bee pollen, psyllium (in laxatives)
Herbal supplements: Echinacea-containing products
Exercise induced anaphylaxis
Asthma masquerading as anaphylaxis
Panic attacks
Munchausen's anaphylaxis
Undifferentiated Somatoform idiopathic anaphylaxis
Histamine-rich foods induced flush (scromboid poisoning).

FINAL DIAGNOSIS
Acute urticaria with Panic Attack/Acute Hyperventilation

CASE REPORT (2)

CHIEF COMPLAINT
"Shortness of breath – feels like throat is closing"
"Finding it hard to get air into the lungs"
"Almost start to hyperventilate" X all been happening over the last 3 years and is worse under stress

HISTORY OF PRESENTING COMPLAINT
38-year-old male, marathon runner, who would notice these symptoms more while running. In his last competition, when he raced towards the last 500m the symptoms got very severe and that was the time he volunteered that "he almost start to hyperventilate". He has been on no medication over the last 3 months.

He has been tried on anti-asthma medications on several occasions but with no improvement, and he had Lung function studies and was told that he did not have asthma, but no alternative diagnosis was given.

PAST MEDICAL HISTORY
No eczema or hay fever.

FAMILY HISTORY
His mother is asthmatic

PHYSICAL EXAMINATION
Peak Flow: 650 l/min

SKIN PRICK TESTS
Revealed that he was non-atopic.

IMPRESSION

Classic case of Hyperventilation Syndrome, with exacerbations due to running and competitions.

Anxiety Disorders
(Classification Based on Anxiety Disorder Association of America)

Most people experience some amount of anxiety and fear in their lifetime. It is a normal part of living. For some people the anxiety and fear are persistent and overwhelming, and can interfere with daily life. These people suffer from anxiety disorder. Anxiety disorders are divided into 5 groups:

1. Panic Disorder
2. Obsessive-Compulsive Disorder
3. Post-traumatic Stress Disorder
4. Generalized Anxiety Disorder
5. Phobias

Panic Attac

A Panic Attack is defined as the abrupt onset of an episode of intense fear or discomfort, which peaks in approximately 10 minutes, and includes at least four of the following symptoms:

A feeling of imminent danger or doom;
The need to escape;
Palpitations;
Sweating;
Trembling;
Shortness of breath or a smothering feeling;
A feeling of choking;
Chest pain or discomfort;
Nausea or abdominal discomfort;
Dizziness or lightheadedness;
A sense of things being unreal, depersonalization;
A fear of losing control or "going crazy";
A fear of dying;
Tingling sensations;
Chills or hot flushes.

There are three types of Panic Attacks:

1. Unexpected – the attack "comes out of the blue" without warning and for no discernable reason.

2. Situational – situations in which an individual always has an attack, for example, upon entering a tunnel.

3. Situationally Predisposed – situations in which an individual is likely to have a Panic Attack, but does not always have one. An example of this would be an individual who sometimes has attacks while driving.

Panic Disorder

Panic Disorder is diagnosed when an individual suffers at least two unexpected Panic Attacks, followed by at least 1 month of concern over having another attack. Sufferers are also prone to situationally predisposed attacks. The frequency and severity of the attacks varies from person to person, an individual might suffer from repeated attacks for weeks, while another will have short bursts of very severe attacks. The sufferer often worries about the physical and emotional consequences of the Panic Attacks. Many become convinced that the attacks indicate an undiagnosed illness and will submit to frequent medical tests. Even after tests come back negative, a person with Panic Disorder will remain worried that they have a physical illness. Some individuals will change their behavioral patterns, avoiding the scene of a previous attack for example, in the hopes of preventing having another attack.

Other symptoms may include headache, cold hands, diarrhea, insomnia, fatigue, intrusive thoughts, and ruminations.
A variant of PD without fear (nonfearful panic disorder [NFPD]) is associated with high rates medical resource use (32-41% of PD patients seeking treatment for chest pain) and poor prognosis.

The literature is full of articles linking hyperventilation with panic attacks, hay fever and asthma (atopy).

A recent study in the USA looking at data from over 3000 concluded "Consistent with previous findings, these data show a relationship between self-reported hay fever and increased likelihood of panic attacks among adults in the general population. The mechanisms of the observed association remain unknown (1)".
It is speculated that having hay fever increases the risk of panic attack, possibly through breathing-related difficulties. It is also possible that irritation of bronchial pathways common in some forms of hay fever increases dyspnoea (shortness of breath) among individuals with panic, further exacerbating both conditions. It is also conceivable that a third unmeasured factor, possibly a genetic, environmental, or personality factor, is associated with the co-occurrence of self-reported hay fever and panic attacks.
Another study looking at the relationship between hyperventilation and paediatric syncope (brief loss of consciousness) shows that "spontaneous hyperventilation could play a role in the pathophysiology of paediatric syncope (2)".
Studies on the pathogenesis of panic disorder (PD) shows that panic disorder runs a chronic or episodic course and panic patients remain clinically unwell between attacks. Panic patients chronically hyperventilate. Evidence from provocation studies suggests that panic patients may have hypersensitive CO2 chemoreceptors. Klein proposed that PD patients hyperventilate to keep pCO2 low (3).
A group from Brazil showed that panic attacks could be induced by hyperventilation. They concluded "The induction of panic attacks by voluntary hyperventilation may be an easy and useful test for validating the diagnosis in some specific panic disorder patients (4).

References
1. Self-reported hay fever and panic attacks in the community, ReneeD. Goodwin, PhD, Annals of Allergy, Asthma, & Immunology 2002; 88:556-559
2. The relationship between hyperventilation and pediatric syncope, Martinon-Torres F, et al, Criticasl Care Division, Santiago de Compostela, Spain, J Pediatric 2001 Jun; 138(6): 894-7
3. Panic, Hyperventilate, and perpetration of anxiety. , Dractu L., Guys Hospital, London, Prog Neuropsychopharmacol Biol Psychiatry 2000
4. Hyperventilation in panic disorder and social phobia. Nardi AE, et al, Lab of Panic Respiration, University of Rio, Brazil, Psychopathology 2001 May-Jun; 34(3): 123-7

Is it Exercise-induced Asthma or Exercise-induced Hyperventilation?

CASE REPORT

CHIEF COMPLAINT
Asthma poorly responsive to high doses of inhaled steroids and 2 courses of prednisone, with poorly controlled ‘Exercise-induced Asthma’ for over 8 months

HISTORY OF PRESENT ILLNESS
A 35-year-old high school rugby coach was referred for an allergic assessment because of persistent "chest tightness" with exercise despite taking Flixotide 750mg twice daily, Salmeterol 50mg twice daily and puffs of ventolin with exercise.

His breathing problems began about 2 years before his visit. At that time he complained of shortness of breath with exertion and was thought to be having exercise-induced asthma. He was started on Flixotide 250 mg twice daily, but this made very little difference to his dyspnea, so his treatment was gradually increased up to what he was taking on presentation. He denied wheezing or coughing, but says on occasions when he exercises he would feel light-headed, associated with his chest tightness. On questioning, he says he has experienced tingling in hands on occasions. These exercise-induced "chest tightness" were poorly responsive to ventolin.

PAST MEDICAL HISTORY
He suffered eczema as a child, and hay fever in his teens.

PHYSICAL EXAMINATION
Peak Flow = 600L/min

SKIN PRICK TEST RESULTS
House dust mite = 10mm, mould = 6mm, cat = 8, grass =8, histamine=5mm

CLINICAL COURSE
The diagnosis of EIA was questioned in view of:

Symptoms despite high doses of Asthma prophylaxis.
No response of symptoms to ventolin.
Light headedness & tingling in fingers.

Hyperventilation was discussed with the patient and he was encouraged to seek physiotherapy assistance for his dysfunctional breathing pattern. He agreed to follow this advice and he was followed up 6 months later and was off all his regular asthma medication and only required ventolin twice in the last 6 months.

FINAL DIAGNOSIS
Mild Asthma with Exercise-induced Hyperventilation (Hyperventilation Syndrome)

DISCUSSION
There seems to be little question that hyperventilation is common in asthmatics and also several patients who get labeled with asthma are suffering from Hyperventilation syndrome. Some of the studies to support this include:

In 1999 a group from University of Iowa examined physiologic changes in airflow and gas exchange that occurred during standardadized treadmill exercise in patients who were previously diagnosed with exercise-induced asthma whose history appeared atypical or where conventional treatment, including an inhaled beta agonist (e.g. ventolin), was ineffective. The study found that chest discomfort perceived as dyspnea during vigorous exercise may be associated with hypocapnia (reduced CO2) from hyperventilation without bronchospasm in children and adolescents previously misdiagnosed and treated as having exercise-induced asthma (1). Exercise-induced asthma or E-I bronchospasm (EIB) occurs in 80 to 90% of individuals with asthma and in approximately 11% of the general population without asthma. It is characterized by post-exercise airways obstruction resulting in a reduction in Peak Flow greater than 10% compared with pre-exercise value. Cold, dry inhaled air during exercise or voluntary hyperventilation is the most potent stimulus for EIB. It was shown in an experiment with dogs, that repeated hyperventilation with dry, cool air causes peripheral airways inflammation, obstruction, hyperreactivity, impaired beta-agonist-induced relaxation. This suggests that other mechanisms in addition to increased smooth muscle tone may contribute to the development of repetitive hyperventilation-induced bronchial obstruction and hyper reactivity (2).

A very famous study published in the BMJ in May 2001, estimated the prevalence of dysfunctional breathing in adults with asthma, treated in the community in Gloucestershire, as about one third of women and a fifth of men (3). Prevalence of dysfunctional breathing in patients treated for asthma in Primary care: cross sectional survey. Thomas M, McKinley RK, et al, Surgery, Gloucestershire, UK, BMJ 2001 May 5; 322): 1098 –1100. The study, in their discussion quite rightly stated: "Our finding of undiagnosed dysfunctional breathing in patients with asthma may also explain the anecdotal reports of efficacy of the Buteyko method. Much publicity has been given to this method, which claims to treat asthma by retraining the breathing pattern to correct hyperventilation. The Buteyko method has, however, had limited scientific scrutiny." (4)

This editorial stimulated some very interesting responses in the BMJ, like:

James Oliver, GP, Cornwall responds: "Physiological hyperventilation is a common finding in patients with mild, symptomatic asthma as shown by raised minute volume of respiration, lowered arterial pCo2 and consequently respiratory alkalosis. This does not in itself imply that such patients are suffering from excessive anxiety. In many cases the desire of an asthmatic patient to breathe deeply can be seen as a natural response to the feeling of restricted breathing. This is entirely analogous to the way in which a patient with eczema develops a habit of scratching, or a patient with mechanical back pain adopts an abnormal posture. In each case the patient’s own behavior, whilst understandable, can nevertheless lead to an exacerbation of the underlying condition. Reviewing the literature there is substantial evidence that hyperventilation itself can lead to significant increases in the resistance of human airways…"

Victoria Johnson, Senior Respiratory Physiotherapist, Nottingham City Hospital writes, " Following a course of physiotherapy treatment, including education, relaxation, breathing control and exercise patients showed improvements in their symptoms and we noted a reduction in respiratory rate."

References
1. Exercise-induced hyperventilation: a psuedoasthma syndrome, Abdel-Hai Hammo & Miles Weinberger, University of Iowa, USA, Ann Allergy Asthma Immunol 1999: 82: 574-578.
2. Repeated hyperventilation causes peripheral airways inflammation, hyper reactivity, and impaired bronchodilation in dogs. Davis MS, Freed AN, Division of Physiology, John Hopkins School of Public Health, USA, Am J Respir Crit Med 2001 Sep 1: 164
3. Prevalence of dysfunctional breathing in patients treated for asthma in Primary care: cross sectional survey. Thomas M, McKinley RK, et al, Surgery, Gloucestershire, UK.
4. Bowler SD, Green A, Mitchell CA. Buteyko breathing techniques in asthma: a blinded randomised controlled trial. Med J Aust 1998; 169: 575-578

SUMMARY:
Hyperventilation Syndrome is very common in the general population and might aggravate symptoms in about one third of asthmatics.
Asthma and Hyperventilation often co-exist.
There is a big overlap between Hyperventilation and Panic Disorder.
Allergic patients (patients with hay fever and asthma) seems to be more prone to hyperventilation than the general population.
Hyperventilation can masquerade as anaphylaxis.
Exercise-induced Asthma can be mistaken for Exercise-induced Hyperventilation.
Hyperventilation Syndrome can be effectively treated with a course of physiotherapy treatment, including education, relaxation and breathing control.

 

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