Case reports

CASE 1

A 38 year old woman presented with difficulty in breathing for 17 years. She had had asthma as a child until the age of seven. She had been symptom free until the age of 21 when she was treated for breathlessness with an inhaled β₂ agonist as required, but due to increasing symptoms a gradual escalation in anti-asthma treatment occurred, including the administration of high dose inhaled corticosteroids. Over the previous two years she had been admitted to hospital on five occasions for breathlessness and was once admitted to the intensive care unit but was not ventilated. Her past history included pulmonary emboli treated by long term warfarin, and hysterectomy for carcinoma of the cervix. Continuous oral prednisolone had been prescribed for three years in varying doses and she had developed hypertension, diabetes mellitus, and back pain thought to be due to osteoporosis. On presentation her prednisolone had been increased to 40 mg orally and she was taking nebulised budesonide (1 mg twice daily), salbutamol 5 mg and ipratropium 500 μg six times a day, bendrofluazide 5 mg, enalapril 20 mg, and insulin in a total dose of 38 units per day. Positive features on examination were expiratory wheezes over the upper thorax. She weighed 96.5 kg (BMI 36.8). Routine clinical investigations showed no abnormalities except an elevated random glucose and glycosylated haemoglobin (table 1). The chest radiograph, ECG and skin prick tests were all normal. Serial twice daily spirometric tests showed poor reproducibility but no significant variability if poor effort was excluded. Formal lung function testing showed a slight decrease from predicted spirometric and lung volumes, but no evidence of obstruction. Flow loop demonstrated poor reproducibility and an upper airway type of obstruction pattern (fig 1, no. 1). Airway resistance by body plethysmography was normal, as were histamine PC₂₀ and arterial blood gas tensions. Bronchoscopic examination showed that the vocal cords adducted during forced expiration and during inspiration, no endobronchial lesion was seen, and no significant eosinophilia was present in the bronchoalveolar lavage. An oesophageal pH monitor indicated that 14.2% of a 24 hour period was spent at a pH <4.0 (normal <4%).

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Table 1

Patient characteristics and indicators of atopy

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Figure 1

Original flow-volume curves from 11 subjects (see table 2, column 1 for subject identity). Curves were transferred from the original using a digital scanner. Many subjects show transient obstruction during expiration.

We concluded that the evidence for asthma was not convincing and that both vocal cord dysfunction and gastro-oesophageal reflux were more likely. As an inpatient she was weaned from all glucocorticosteroids. She was able to leave hospital on no regular anti-asthma medication without change in her spirometric values and with improved control of her diabetes and hypertension. Her gastro-oesophageal reflux was treated by dietary advice and initially omeprazole, but this was associated with a rash and cimetidine was substituted. She remained on no regular inhaled medication six months after withdrawal of her prednisolone.

Results

All subjects were invited back for review of their asthma to complete the above list of investigations, but not all agreed to attend despite repeated requests. Table 1 lists the patient details. The subjects were more likely to be female (13:1), four were health care workers, and 11 reported multiple diseases, particularly dysmenorrhoea. Two reported a past history of sexual abuse. Nine were obese (BMI >25), two had morbid obesity, while eight had smoked and at least nine had atopy. A mean of 6.9 admissions per year had occurred over the preceding two years with one individual being admitted over 44 times/year.

Table 2 lists the relevant investigations. All showed PEF variability, but only five had an obstructive pattern on spirometric testing (most showing a reduction in both FEV₁ and FVC, data not shown). Only two patients had a bronchodilatation of ⩾20% to β₂ agonists and, of the seven tested by plethysmography, all had normal airway conductance (sGaw). Both patients 1 and 2 had a histamine PC₂₀ within the normal range, but unfortunately most of the others did not have this test performed.

Figure 1 shows the flow loops available on these patients. Those depicted are the most consistent of many attempts. It can be seen that there is often transient expiratory obstruction which could lead to a decrease in the value of the FEV₁. The most common expiratory pattern seen has the appearance of rhythmic closure and opening of the vocal cords in expiration (nos 2, 5, 6, 8, and 12 in fig1). These are suggestive of transient obstruction followed by expiratory overshoot. This can be a feature of vocal cord dysfunction. Table 2 also lists the other tests which led to diagnoses other than asthma.

Discussion

It is evident that the patients described above belong to a heterogeneous group. The majority do not, however, have typical features of asthma. Some evidently have hyperventilation, others have gastro-oesophageal reflux or sleep apnoea, while some have psychiatric disease. A number of the patients had undergone intubation and ventilation, which in most cases was associated with a low Paco ₂, perhaps representing hyperventilation and vocal cord dysfunction, while one ventilated individual was hypoxaemic and had sleep apnoea.

On the basis of their symptoms and PEF measurements, all of these patients described would fit the diagnosis of asthma according to the criteria of the American Thoracic Society,7 in as much as they exhibited variable airways obstruction, sometimes improving after β₂ agonists, particularly when PEF alone was used. Nine of the 14 did not have airway obstruction from their FEV₁:FVC ratio, while of seven tested for airway conductance, none had objective lower airway obstruction. Some had upper airway obstruction at the level of the larynx as judged by observation of the vocal cords or the pattern of the flow-volume loop. The inability to perform spirometric tests reproducibly, either on a simple dry wedge spirometer or as a flow-loop procedure, would suggest that upper airway closure could be the problem, indicating vocal cord dysfunction. In contrast, it is difficult to assess PEF effort and it is easy to manipulate the readings to either under or over-read and, in addition, variable effort may be mistaken for true PEF variability. Asthmatic subjects are, however, able to give consistent PEF and spirometric readings even in the presence of relatively severe obstruction.

Psychological aspects of asthma have attracted attention over the years, with some studies suggesting that asthmatic patients may have more personality problems than normal subjects, while other studies have implied that psychological disorders are no more common than would be expected for those suffering from a chronic disease.9It has become apparent, however, that a small number of patients have upper airway wheezing which is unrelated to asthma, and appears to be paradoxical laryngeal adduction during both expiration and inspiration. This vocal cord dysfunction may be associated with psychological disturbance and multiple diseases.10 ,11

Patients with SRA appear to have marginal therapeutic gain from treatment with steroids, but nonetheless are often given high doses of oral glucocorticoids to counteract their symptoms. It is therefore essential that patients who either have asthma that is difficult to manage, or require frequent and high doses of steroids or frequent hospital admission, have a critical reassessment of their diagnosis and review of their investigations. As experienced by the referring physicians, we found these patients difficult to manage and to assess, as can be seen by the tentative diagnoses in table 2. Some patients may appear to satisfy the definition of SRA but, upon review, probably do not have severe asthma at all. It is essential to identify patients with both true SRA and those with “pseudo-SRA” as the latter may mask a treatable disorder which is not asthma.

While our patients were not assessed by a protocol, having reviewed the above cases we would suggest the following as an assessment for those with difficult to manage or apparent “steroid resistant asthma” (see also Woolcock4):

(1)

does the patient definitely have asthma?—reproducible expiratory manoeuvre and FEV₁ /FVC ratio of <70% or flow-volume curves and appropriate airway obstruction (not PEF measurements);

(2)

20% reversibility of FEV₁ (not PEF) to 200 μg salbutamol;

(3)

airway conductance/resistance;

(4)

histamine or methacholine challenge with PC₂₀ result in appropriate range for asthma;

(5)

assessment of delivery of inhaled drugs and compliance;

(6)

bronchoscopy: assess movement of vocal cords on inspiration and expiration, bronchoalveolar lavage for eosinophils and differential cytology, biopsy for submucosal basement membrane thickening and to exclude endobronchial tumour;

(7)

three week 0.5 mg/kg prednisolone trial with repeated measures of FEV₁, bronchial hyperreactivity and drug compliance;

(8)

investigations to exclude other treatable diseases: sleep study, 24 hour pH monitoring, hyperventilation test, psychological testing, etc.