Conditions Mimicking Asthma In The Adult Population

Luis F. Laos, M.D. and James D. Cury, M.D.
Luis F. Laos, M.D. is an Assistant Professor, Department of Pulmonary and Critical Care,
at the University of Florida Health Science Center / Jacksonville.
James D. Cury, M.D. is an Associate Professor and Chief, Division of Pulmonary
and Critical Care, at the University of Florida Health Science Center / Jacksonville.

Asthma affects 7% of the population of the United States at one time or another and 4% of the population requires prolonged therapy for asthma. The cost of asthma in the U.S. is over $5 billion dollars a year. Over 1/2 of this cost is felt to be unnecessary as it is incurred in what is thought to be preventable circumstances chiefly emergency department visits and hospitalizations. The prevalence of asthma is increasing as is the mortality. These epidemiologic facts have caused a great deal of attention to be focused on asthma. This focus has caused a much greater awareness in the community about asthma in both patients, physicians, and managed care overseers. This awareness has both caused an increase in the diagnosis of asthma and also an increase in the recognition that many conditions mimic asthma.

The National Heart, Lung, and Blood Institute published the Guidelines for the Diagnosis and Management of Asthma in May 1997. This report emphasized objective lung function measurements to diagnose and manage asthma. They define asthma as a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and in the early morning. These episodes are usually associated with widespread but variable air flow obstruction that is often reversible either spontaneously or with treatment.

Usually asthma is suspected in an individual with wheezing. Unless the history and physical exam clearly define the cause of the wheeze, the airways should be evaluated. The easiest, most available means to evaluate the airways is by having the patient perform spirometry with careful attention to the flow/volume loop. The airways can be divided into three anatomic areas that have different physiologic characteristics which may allow the site of obstruction to be determined. The three areas are the large extrathoracic airways which include the mouth and nose down to the level of and including the extrathoracic trachea, the large intrathoracic airways which begin at the level of the intrathoracic trachea and extend to the level of the 2mm airways and the small airways which begin at the 2mm airways (beyond the 8th and 9th branches off the trachea) and extend to the periphery. Table 1 while not an exhaustive list, describes the more frequent causes of wheezing.

Upper airway conditions that cause wheezing are frequently not recognized. Post nasal drip syndrome (PNDS) from a variety of reasons (sinusitis, rhinitis, allergy) is the most common upper airway condition causing wheezing. The common cold is the most common disease affecting mankind. Wheezing can occur in up to 11% of people with a cold. The mechanism that a cold causes wheezing is PNDS. PNDS should be considered to be the cause of wheezing when a patient describes a throat tickle or that something is dripping down their throat. PNDS should be suspected in patients who constantly clear their throat.

Vocal cord dysfunction syndrome is a syndrome in which the vocal cords paradoxically adduct during inspiration. This disorder causes a monophonic inspiratory wheeze heard loudest over the glottis. It is diagnosed by laryngoscopy in an unsedated patient. It is felt to be a type of conversion reaction and is thus non-volitional. The National Jewish Hospital in Denver has found that up to 9% of its referrals for refractory asthma were due to vocal cord dysfunction syndrome.

Laryngeal or upper airway edema due to hereditary angioneurotic edema, angiotensin converting enzyme inhibitor (ACEI) drugs, and anaphylaxis also are upper airway causes of wheezing. Hereditary angioneurotic edema is a C-1 esterase deficiency. Swelling of the tongue or lips with an inspiratory wheeze (stridor) in patients that are taking ACEI should prompt discontinuation of the class of drugs unless an obvious alternate cause can be found. Anaphylaxis can cause both upper airway and lower airway obstruction. There are also several causes of lower airway obstruction (wheezing) that are not asthma. Edema fluid in the interstitial space of the airway causes airway narrowing and thus causes wheezing (so called "cardiac asthma"). Pulmonary emboli cause wheezing at times due to a variety of mechanisms. Retained secretions and cellular elements can obstruct small airways and cause wheezing in people with bronchiectasis, bronchitis, or bronchiolitis. Aspiration with subsequent airway obstruction also causes wheezing.

Upper airway obstruction from any of the causes in Table 1 causes characteristic changes in the flow volume loop that distinguish them from lower airway obstruction. All intrathoracic airways lengthen and get wider with inhalation while extrathoracic airways because of a negative intraluminal pressure want to get shorter and narrower. With exhalation, intrathoracic airways get shorter and narrower while extrathoracic airways tend to get longer and wider.

If a large airway obstruction (occurring from the hypopharynx to the carina) allows the wall of the airway to vary with the breathing cycle then the obstruction to airflow is greatly enhanced depending upon the phase of the breathing cycle. If airflow obstruction occurs only during inhalation, then the obstruction is called variable extrathoracic large airway obstruction (Figure 1). This is noted by a blunt inspiratory loop on the flow/volume loop performed with maximum effort. Variable extra thoracic large airway obstruction can be seen with any lesion occurring from the hypopharynx to the level of approximately the sternal notch. This pattern can be seen with vocal cord dysfunction, vocal cord paralysis, epiglottitis, or any cause of laryngeal edema (ACEI, anaphylaxis, hereditary angioneurotic edema).

If the obstruction to airflow only occurs during the exhalation limb of a flow/volume loop that is performed with maximum effort then the obstruction is called a variable intrathoracic large airway obstruction (Figure 2). This pattern can be caused by any process which affects the trachea from approximately the level of the sternal notch to the carina. This pattern is more uncommon but can be caused by tumors, chondromalacia, Wegener's granulomatosis, infection or compression of this segment of the trachea.

If a process that causes obstruction fixes the airway wall so that it cannot vary with the breathing phase then the obstruction is called a fixed large airway obstruction (Figure 3). This process causes both the inhalation and exhalation limbs of the flow/volume loop to be blunted. Any of the above pathologic conditions can cause this pattern.

The flow/volume loop caused by lower airway obstruction is very different from the loops seen with large airways obstruction (Figure 4). The causes of lower airway obstruction cause varying degrees of obstruction in multiple scattered sites. This causes the shape of the flow/volume loop seen in Figure 4. The diagnosis of asthma can be made in three ways. A 12% and 200cc increase (or more) in forced expiratory volume in one second seen on spirometry after inhaling a short acting bronchodilator is highly suggestive of asthma. Likewise, a fluctuation of 20% or more in daily peak flow volumes or between symptomatic and asymptomatic periods suggests the presence of asthma. A bronchoprovocation test can also be used to diagnose asthma but it is not usually needed.

Figure 1. Flow / volume loop 1 is normal. Flow / volume loop 2 is a variable extrathoracic large airway obstruction.	Figure 2. Flow / volume loop 1 is normal. Flow / volume loop 2 is a variable intrathoracic large airway obstruction.	Figure 3. Flow / volume loop 1 is normal. Flow / volume loop 2 is a fixed large airway obstruction.	Figure 4. Flow / volume loop 1 is normal. Flow / volume loop 2 is indicative of small airways obstruction.

In summary, spirometry with flow/volume loop should be performed in all patients with wheezing where the history and physical exam and response to therapy do not reveal an obvious cause.

REFERENCES

This article is a compilation of data taken from the sources listed below.

1. National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma. Bethesda, MD; National Institutes of Health; 1997. NIH publications 97-4051.
2. Smyrnios NA, Irwin RS. Wheeze. From Irwin RS, Curley FJ, Grossman RF (eds): Diagnosis and Treatment of Symptoms of the Respiratory Tract. Armonk, New York, Futurn Publishing Company, Inc. 1997.
   

Jacksonville Medicine / November, 1999