The Role of Multislice in Assessment of Resistant and Atypical Asthmatic Cases

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1 Med. J. Cairo Univ., Vol. 80, No. 2, December: 35-4, The Role of Multislice in Assessment of Resistant and Atypical Asthmatic Cases YOUSSRIAH Y. SABRI, M.D.; MARIAN F. FARID, M.D. and SARA M.K. ALI, M.Sc. The Department of Radiology, Thoracic Imaging Unit, Faculty of Medicine, Cairo University Abstract Background: Bronchial asthma is considered one of the most common chest diseases causing recurrent wheezes. With the new advances in computed tomography machines, it is now possible to understand the underlying pathophysiologic changes affecting the airways of the asthmatic patients. Multislice computed tomography (MSCT) plays an important role in assessing the patient s response to treatment. MSCT is used also for identification of causes of failure to respond to asthma medications which include complicated asthma and presence of conditions that may be confused with asthma. Aim of the Work : The aim of our review study is to evaluate the role of multislice CT in detecting and characterizing lung findings in resistant cases of bronchial asthma, complicated and atypical cases. Patients and Methods: This study involved 20 patients; 0 males and 0 females, age range 6-80 (average of 42.2years) from June 200 till November 20. All patients were known or clinically suspected cases of bronchial asthma. One of the cases was known to be Churg-Strauss. All cases were not responding to therapy. Cases were referred to radiology department in kasr El- Ainy for MSCT. They all presented with persistent or recurrent attacks of chronic productive cough and dyspnea. Wheeze was the main complaint in 2 patients. Three patients also had fever. They were all subjected to Thorough clinical examination with history taking, general and chest examination, Pulmonary function tests (PFT), laboratory tests mostly complete blood picture, the other tests were considered according to case e.g. Assessment of serum immunoglobulin, sputum culture..etc. MSCT was done to all patients. Results : In this study, we provide evidence that multislice computed tomography (MSCT) especially using the HRCT technique is useful in patients with chronic or recurring symptoms of asthma especially those who are resistant to treatment. We found that MSCT can demonstrate a number of findings that support the diagnosis of asthma (8 out of 20 patients) or suggest an alternative diagnosis which may mimic asthma clinically, which in our study was hypersensitivity pneumonitis ( case) and congestive heart failure ( case). In those patients who are radiologically proved to be asthmatics, the MSCT was helpful in detecting the cause of non response to treatment which is the presence of irreversible airway Correspondence to: Dr. Youssriah Y. Sabri, The Department of Radiology, Faculty of Medicine, Cairo University changes or the presence of complications (allergic bronchopulmonary asperigillosis) ABPA in our study in 4 out of 8 patients, including the treatment (steroid) complications. We found that peribronchial thickening and hyperinflation are the most common MSCT findings (4 out of 20 patients) and (3 out of 20 patients), respectively. Other findings are mucus plugging, bronchiectasis and bronchial narrowing. Key Words: Multislice computed tomography Bronchial asthma Resistant bronchial asthma. Introduction ASTHMA is a syndrome in which there are many triggers that produce the final result of bronchoconstriction []. Asthma triggers are substances or conditions that can lead to a worsening of asthma. These can be inorganic, organic, or biochemicals derived from nonliving or living entities; high, low, or changes in surrounding temperature; exercise; infectious agents; postnasal drip or sinus drainage; or possibly even changes in stress level [ 2 ]. The asthma is characterized by reversible airway obstruction, bronchial hyper-responsiveness (BHR), and air way inflammation. The air way obstruction is reversible, but may be incomplete or they may be actually fixed airway obstruction. Partially reversible or fixed airway obstruction brings the concept of airway remodeling in asthma. That is, structural changes develop in the airways to inhibit complete airway dilatation []. Asthma attacks can last for minutes to days, and can become dangerous if the airflow is severely restricted [2]. Many other diseases should be considered in the differential diagnosis of bronchial asthma because of their frequency and clinical significance. These include: Chronic obstructive pulmonary disease (COPD), hyperventilation, aspiration, la- 35

2 36 The Role of Multislice in Assessment of Resistant Asthma ryngeal changes/vocal cord dysfunction, pneumothorax, cystic fibrosis (CF), cardiac diseases, e.g., left heart failure, pulmonary embolism, gastroesophageal reflux disorder (GERD) [3]. CT helps differentiation between these diseases. The other clinical indications for CT in patients with asthma include detection of bronchiectasis in patients with suspicion of allergic bronchopulmonary aspergillosis; documentation of the presence and extent of emphysema in smokers with asthma; and identification of conditions, such as hypersensitivity pneumonitis, that may be confused with asthma [4]. Bronchial dilatation, bronchial wall thickening, mucoid impaction, centrilobular bronchiolar abnormalities, patchy areas of mosaic perfusion, and regional air trapping on expiratory scans may be identified on high-resolution CT (HRCT) in patients with uncomplicated asthma, the severity of these abnormalities correlates with the severity of asthma [4,5]. Aim of the work : The aim of our review study is to evaluate the role of HRCT in detecting and characterizing airway changes in resistant cases of bronchial asthma, complicated and atypical cases. Material and Methods This study included 20 patients; 0 males and 0 females, age range 6-80 (average of 42.2 years). All patients were known or clinically suspected cases of bronchial asthma. One of the cases was known to be Churg-Strauss. All cases were not responding to therapy. Cases were referred to radiology department in kasr El- Ainy for MSCT. They all presented with persistent or recurrent attacks of chronic productive cough and dyspnea. Wheeze was the main complaint in 2 patients. Three patients also had fever. All patients were subjected to: Thorough clinical examination with history taking, general and chest examination. Pulmonary function tests (PFT). Laboratory tests mostly complete blood picture, the other tests were considered according to case e.g. assessment of serum immunoglobulin, sputum culture..etc. HRCT: GE Light Speed Plus MSCT 4 channels set present in the Radiology department Kasr El-Ainy was used for all cases. See (Table ) for HRCT technique used. Table (): HRCT technique used in Kasr El-Ainy. Scout Kv20 Holding breath ma20 HRCT Protocol Scan type Helical full 0.5 sec Detector Row 4 Helical Thickness.25 Pitch.5: Speed(mm/rot) 7.5 Detector configuration 4X.25 Beam collimation 5.0 Interval mm.0 Gantry tilt 0.0 FOV Depends on patients size Kv ma Total exposure time 6-20 Holding breath in full inspiration Reconstruction type STD (standard) Mediastinal window images are also taken Results PFT showed reduced FEV and reduced ratio of forced expiratory volume (FEV)/functional respiratory capacity (FVC) (<0.7) in all of the 8 patients showing HRCT findings suggestive of asthma or complicated asthma and in the patient were HRCT suggested HP. Normal ratio was detected in the patient with HRCT diagnoses of congestive heart failure (CHF). 3 Cases diagnosed as ABPA showed positive serum precipitins (IgG) against. Aspergillus, while one case had aspiration, cytology and culture and was proved to be Aspergillus Fumigatus. The case with therapy complications and suggested superadded infection was proved to be tuberculin positive and sputum was positive for acid-fast bacilli. Table (2): Summary of HRCT findings in our 20 cases. HRCT Finding Hyperinflation Peribronchial thickening Bronchiectasis Bronchial narrowing Mucus Plugging Atelectasis/consolidation Centrilobular emphysema Air-trapping Centrilobular nodules & tree-in-bud pattern Mosaic perfusion Prominent interlobular septae Pleural effusion Pleural thickening Lung nodules Ribs fracture Mediastinal lipomatosis No. of cases

3 (A) Youssriah Y. Sabri, et al. 37 Fig. (): 48 year-old male patient known asthmatic presenting with chronic productive cough, wheeze and dyspnea. HRCT showing hyperinflation, peribronchial thickening, narrow lumen (arrow) and centrilobular nodules. Fig. (4): 5 year-old female patient known asthmatic presenting with chronic productive cough, wheeze and dyspnea. HRCT showing air-trapping (arrow) and tree in bud appearance. Fig. (2): 55 year-old male patient known to be asthmatic, presenting with chronic productive cough, wheeze and dyspnea. HRCT showing mosaic pattern (arrow) with hyperinflation, peribronchial thickening and narrow lumen. Fig. (3): 46 year-old female patient known asthmatic presenting with chronic productive cough and wheeze. HRCT showing centrilobular nodules and tree-in-bud pattern (arrows) denoting small air-way disease. Fig. (5A,B): 80 year-old male patient known asthmatic and chronic heavy smoker for 60 years presenting with chronic productive cough, dyspnea and wheeze. HRCT shows centrilobular emphysema, peribronchial thickening, bronchiectasis (arrow) and bilateral pleural thickening.

4 38 The Role of Multislice in Assessment of Resistant Asthma Fig. (6): 40 year-old male patient known asthmatic presenting with chronic productive cough, dyspnea and fever. Non-Enhanced mediastinal window image show hyperdense tubular lesions representing mucus plugging of dilated bronchi (arrow) in the right middle lobe which shows consolidation and retracted fissure suggesting decrease volume. The case was aspirated, culture and sensitivity revealed Aspergillus fumigates (ABPA). Fig. (8): 60 year-old female patient suspected to be asthmatic, presenting with progressive dyspnea and chronic cough. HRCT showing diffuse ground glass opacification with areas of air trapping; findings are highly impressive of subacute hypersensitivity pneumonitis. History taking showed that the patient is a bird breeder. PFT showed mixed pattern of restrictive and obstructive changes. (A) (A) (B) Fig. (7A,B): 6 year-old female patient known asthmatic diagnosed as Churg-Strauss, complaining of chronic productive cough, wheeze and dyspnea. HRCT showing hyperinflation, peribronchial thickening and lumen compromise. (B) Fig. (9A,B): 65 year-old female patient suspected to be asthmatic, presenting with dyspnea and cough. Case of CHF, HRCT showing bilateral effusion, prominent interlobular septa denoting interstitial edema. Sagittal image shows major fissure effusion

5 Youssriah Y. Sabri, et al. 39 (in 3 out of the 4 patients) and patchy consolidation (in all the 4 patients). These findings are more or less consistent with the study by Khan AN [7] who found that bronchiectasis and peribronchial thickening are the most common CT scan findings in allergic bronchopulmonary aspergillosis but he found that high-attenuating mucoid impaction is present in as many as 30% of patients, compared to 75% of patients in our study. This discrepancy may be due to the limited number of patients in our study. Fig. (0): 29 year-old female patient known asthmatic presenting with dyspnea and chronic cough and chest pain. Patient under corticosteroid therapy. CT revealed multiple rib fractures (arrow) noted and lung nodules suggesting bony complications of corticosteroids and super added chest infection Discussion Although HRCT is more costly than chest radiography and exposes the patient to more radiation however, CT scans can demonstrate a number of findings that support the diagnosis of asthma. HRCT remains the most sensitive study for morphologic changes associated with asthma [6]. In this study, we provide evidence that multislice computed tomography (MSCT) especially using the HRCT technique is useful in patients with chronic or recurring symptoms of asthma especially those who are resistant to treatment. We found that MSCT can demonstrate a number of findings that support the diagnosis of asthma (8 out of 20 patients) or suggest an alternative diagnosis which may mimic asthma clinically, which in our study was hypersensitivity pneumonitis ( case) and congestive heart failure ( case). In those patients who are radiologically proved to be asthmatics, the MSCT was helpful in detecting the cause of non response to treatment which is the presence of irreversible airway changes or the presence of complications (ABPA in our study in 4 out of 8 patients) including the treatment (steroid ) complications. We found that peribronchial thickening and hyperinflation are the most common MSCT findings (4 out of 20 patients) and (3 out of 20 patients), respectively. Other findings are mucus plugging, bronchiectasis and bronchial narrowing. In patients who are diagnosed as ABPA, the most prominent HRCT features found were bronchiectasis (in all the patients), bronchocele (in 3 out of the 4 patients), hyperdense mucus plugging Bronchial wall thickening is a common feature of severe asthma. Walker et al. [8] reported a prevalence of 62% and others have found bronchial wall thickening to be more prevalent in asthma patients compared with healthy controls, and associated with asthma severity and longer disease duration. Various studies have utilized CT for noninvasive quantitative assessment of proximal airway structural changes in asthmatic adults and children [9]. De Blic et al. [0] demonstrated, in children with severe asthma, a correlation between bronchial wall thickening and reticular basement membrane thickness, Saglani et al. did not []. Other studies have shown that asthma patients have increased airway wall thickness regardless of disease severity [9] ; whereas others have demonstrated a correlation between CT-assessed airway remodeling and asthma severity [2]. However, there is some inconsistency between researchers on the airway lumen in asthma. Niimi et al. [3] reported no significant difference in lumen area of asthma patients of varying severity and healthy controls. Gupta et al. [4] on the other hand, demonstrated that the right upper lobe apical bronchus (RB) lumen area was significantly narrowed, in 99 severe asthma patients, compared with healthy individuals. In asthma, airway wall thickening has been correlated with airflow limitation, airway hyperresponsiveness, and air trapping on expiratory CT. The small airways (peripheral membranous bronchioles less than 2mm in diameter) are also significantly affected in asthma, with the presence of significant inflammation and airway remodeling being demonstrated in the small airways of asthma patients. CT scanners, however, cannot be used for the direct evaluation of the dimensions of the small airways as they are beyond the currently available resolution. Indirect changes caused by the small airways on the lung parenchyma can however be detected on CT, as small airways dysfunction results in reduced ventilation of part of the lung, which results in a reflex reduction in perfusion highlighted as areas of decreased attenuation on CT images. Heterogeneity of lung atten-

6 40 The Role of Multislice in Assessment of Resistant Asthma uation in asthma can be noticeably accentuated in expiratory scans compared with inspiratory CT scans, due to regional differences in small airway closure or emptying rate. Air trapping has been shown to correlate with asthma severity [5], yet the relationship is not fully understood. Busacker et al., found that individuals with air trapping were significantly more likely to have a history of asthma-related hospitalization and intensive care visits compared with those without air trapping, which suggests that CT-assessed air trapping could potentially be used to identify the 'at-risk' asthma phenotype [6]. CT-assessed air trapping has also been associated with airway hyperresponsiveness, disease duration, airflow limitation, and evaluation of response to inhaled corticosteroid therapy [7]. In the present study, 5 out of the 20 patients were found to have air trapping, this is consistent with the study conducted by Mikos et al. [8]. Using a manual method, where he showed that focal and diffuse air trapping (E/I ratio) correlated with airway wall thickness (WA%). Focal air trapping was significantly increased in a subgroup of 0 asthmatics patients with normal FEV % predicted and FEV /FVC%. In a recent study from the Severe Asthma Research Program the extent of gas trapping measured using lung densitometry was associated with increased hospitalization and those with the most severe gas trapping were also those most likely to need treatment in the intensive care unit [6]. These studies, especially in asthma, have shown that these measurements of gas trapping do correlate with clinical symptoms in severe asthmatics and in response to therapy [9]. In this study, 8 out of the 20 patients were found to have bronchiectasis, 4 of them were proved to have ABPA, this is consistent with the study conducted by Gupta et al. [4] who found that in a cohort of 85 severe asthma patients, the prevalence of bronchiectasis was 40%, which was similar to the median of the reported studies of 3%. Bronchiectasis in asthma patients was associated with longer disease duration and poorer lung function [20]. However, association with disease severity was found in some studies but not in others [2]. Whether or not bronchiectasis in severe asthma is a co-morbidity, resulting in 'difficult' to manage asthma, or represents structural change or remodeling with natural progression of the disease is not known, and longitudinal studies are required to ascertain this differentiation [8]. Investigators in early studies used HRCT findings to prove that bronchial dilatation was prevalent in 4% of the pulmonary lobes in 8 patients with asthma who had clinical and immunologic evidence of ABPA and in 5% of lobes studied in 8 patients with asthma who had positive skin test results for only Aspergillus fumigatus. The authors speculated that the unexpected findings in individuals with asthma alone may have been due to steroidal suppression of immunologic markers in these patients who actually had ABPA, non-aspergillus fungal disease, or cylindrical bronchiectasis [6]. As regarding the value of HRCT in asthmatic patients with ABPA, a study of the value of thoracic HRCT in demonstrating central bronchiectasis in ABPA was proven in all 2 patients with the disease and in most of the segments. Central and peripheral bronchiectasis, but not peripheral bronchiectasis alone, have been evaluated by using both chest radiography and HRCT images as a diagnostic criteria for ABPA. One of the studies showed that HRCT scan is more sensitive than radiography for diagnosing bronchiectasis. In this study, bronchiectasis was identified in 4/7 ABPA patients (82%), pleural thickening in 4 (82%) and atelectasis in 9 (64%). However, patients with bronchiectasis and asthma do not necessarily have ABPA, although both conditions are present in about 80% of ABPA [22]. Mucoid impaction is a well-defined finding in patients with ABPA. It may appear as centrilobular bronchiolar plugging or have a tree-in-bud appearance on HRCT scans. Mucoid impaction is believed to be one of the physiologic origins of mosaic lung attenuation [6]. In a study by Ward et al. [23] who compared the high-resolution CT findings in 44 asthmatic patients with ABPA and 38 asthmatic patients without ABPA. Abnormalities seen more commonly in patients with ABPA included bronchiectasis, centrilobular nodules, and mucoid impaction. Bronchiectasis was present in 95% of patients with ABPA; centrilobular nodules, in 93%; and mucoid impaction, in 67%. By comparison, bronchiectasis was detected in 29% of the asthmatic control group; centrilobular nodules, in 28%; and mucoid impaction, in 4%. Mitchell et al. [24] compared the highresolution CT scans obtained in 9 patients with documented ABPA with scans obtained in 8 asthmatic control subjects. Seventeen patients (89%) with ABPA had central cystic or varicose bronchiectasis typically involving several lobes. By comparison, only three asthmatic patients (7%) had bronchiectasis, and it was exclusively cylindrical in nature. One of the great limitations in our study is the limited capability of the equipment used (MDCT

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