Download Background: Bronchial asthma is considered one of the most

The Role of Multislice in Assessment of Resistant
and Atypical Asthmatic Cases.
Youssriah Yahia Sabri ,MD MSc, Marian Fayek Farid, MD MSc, Sara Mahmoud Kamel Ali, M.B.B.CH.
Radiology Department, Thoracic Imaging Unit, Kasr Al-Aini, Cairo University, Cairo, Egypt.
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; 10 males and 10 females, age range 1680 (average of 42.21years) from June 2010 till November 2011. 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 12 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 (18 out of 20 patients) or suggest an
alternative diagnosis which may mimic asthma clinically, which in our study was hypersensitivity
pneumonitis (1 case) and congestive heart failure (1 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 (allergic
broncho-pulmonary asperigillosis) ABPA in our study in 4 out of 18 patients, including the treatment
(steroid) complications. We found that peribronchial thickening and hyperinflation are the most
common MSCT findings (14 out of 20 patients) and (13 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 (1). 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 (1).
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, laryngeal 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.
Patients and methods
Patients:
This study included 20 patients; 10 males and 10 females, age range 16-80 (average of 42.21years). 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 12 patients .Three patients also had fever.
Methods:
All patients were subjected to
1) Thorough clinical examination with history taking, general and chest examination.
2) Pulmonary function tests (PFT).
3) Laboratory tests mostly complete blood picture, the other tests were considered according to case e.g.
assessment of serum immunoglobulin, sputum culture..etc.
4) HRCT:
GE Light Speed Plus MSCT 4 channels set present in the Radiology department Kasr El-Ainy was used
for all cases. See table 1 for HRCT technique used.
Table 1: HRCT technique used in Kasr El –Ainy
Scout
Kv120
mA20
Holding breath
HRCT Protocol
Scan type
Helical full 0.5 sec
Detector Row
4
Helical Thickness
1.25
Pitch
1.5:1
Speed(mm/rot)
7.5
Detector configuration
4X1.25
Beam collimation
5.0
Interval
1.0
mm
Gantry tilt
0.0
FOV
Depends on patients’ size
Kv
120-140
mA
120-160
Total exposure time
16-20
Holding breath in full inspiration
Reconstruction type
STD(standard)
Mediastinal window images are also taken
RESULTS
PFT showed reduced FEV1 and reduced ratio of forced expiratory volume (FEV1)/ functional respiratory
capacity (FVC) (<0.7) in all of the 18 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 shows summary of the HRCT findings in our 20 cases.
HRCT finding
No. of cases
Hyperinflation
13
Peribronchial thickening
14
Bronchiectasis
8
Bronchial narrowing
6
Mucus Plugging
4
Atelectasis/consolidation
4
Centrilobular emphysema
1
Air-trapping
5
Centrilobular nodules& tree-in-bud pattern
3
Mosaic perfusion
2
Prominent interlobular septae
1
Pleural effusion
1
Pleural thickening
1
Lung nodules
1
Ribs fracture
1
Mediastinal lipomatosis
1
Fig (1): 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 (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 (4): 51 year-old female patient known asthmatic presenting with chronic productive
cough , wheeze and dyspnea. HRCT showing air-trapping (arrow) and tree in bud
appearance.
a
b
fig 5 (a, 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.
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 7 (a, b): 16 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.
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.
Fig 9 (a, 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
Fig 10: 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.
DISCUSION
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 (18 out of 20 patients) or suggest an alternative diagnosis which may mimic
asthma clinically, which in our study was hypersensitivity pneumonitis (1 case) and congestive heart
failure (1 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 18 patients) including the treatment (steroid
) complications. We found that peribronchial thickening and hyperinflation are the most common MSCT
findings (14 out of 20 patients) and (13 out of 20 patients), respectively. Other findings are mucus
plugging, bronchiectasis and bronchial narrowing.
In the 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
(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 highattenuating 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.
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. (10) demonstrated, in children with severe
asthma, a correlation between bronchial wall thickening and reticular basement membrane thickness,
Saglani et al. did not (11). Other studies have shown that asthma patients have increased airway wall
thickness regardless of disease severity (9) ; whereas others have demonstrated a correlation between CTassessed airway remodeling and asthma severity (12). However, there is some inconsistency between
researchers on the airway lumen in asthma. Niimi et al. (13) reported no significant difference in lumen
area of asthma patients of varying severity and healthy controls. Gupta et al., (14) on the other hand,
demonstrated that the right upper lobe apical bronchus (RB1) 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 hyper-responsiveness, 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 attenuation 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 (15), 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 (16). CT-assessed air trapping has also been associated with airway
hyperresponsiveness, disease duration, airflow limitation, and evaluation of response to inhaled
corticosteroid therapy (17).
In our study also, 5 out of the 20 patients were found to have air trapping ,this is consistent with the
study conducted by Mikos et al (18). 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 10 asthmatics patients with normal FEV1% predicted and FEV1/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 (16).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 (19).
In our study also 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. (14) who found that in a cohort
of 185 severe asthma patients, the prevalence of bronchiectasis was 40%, which was similar to the
median of the reported studies of 31%. 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 (21). 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 41% of the pulmonary lobes in 8 patients with asthma who had clinical and immunologic
evidence of ABPA and in 15% 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 21 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 14/17 ABPA patients (82%), pleural
thickening in 14 (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 high-resolution CT
scans obtained in 19 patients with documented ABPA with scans obtained in 18 asthmatic control
subjects. Seventeen patients (89%) with ABPA had central cystic or varicose bronchiectasis typically
involving several lobes. By comparison, only three asthmatic patients (17%) 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 4
slice); while the minimum requirements for quantitative assessment of the airway wall thickness and
evaluation, is MDCT 16 slice. Most of the findings were based on visual assessment, which may lead to
inter-observer difference in interpretations of the findings. So, more studies with the up to date
equipments are required.
References
1. Newell JD, Chan ED, Martin RJ: Imaging of diffuse airway diseases. Imaging of diffuse lung
disease.2000;6:171- 174
2. Hopp RJ and Townley RG: The Origins and Characteristics of Asthma. A Guide for Practical
Understanding and Treatment, Fifth Edition. 2006;1:3-30
3. Ukena D, Fishman L, and Niebling WB: Bronchial Asthma: Diagnosis and Long-Term
Treatment in Adults. Dtsch Arztebl International journal, May 2008; v.105 (28-29).
4. Grenier PA, Aubry CB, and Brillet PY: Asthma. CT of the Airways 2008;10:239-254.
5. Castagnaro A, Rastelli A, Chetta A, et al: High-resolution computed tomography evaluation of
airway distensibility in asthmatic. Radiol Med (Torino) (2008) 113: 43-55.
6. Canaday PG and Lin EC: Asthma Imaging .Medscape reference Sept 2011.
7. Khan AN: Thoracic Aspergillosis Imaging. Medscape reference ,May 2011.
8. Walker C , Gupta S, Raj V, et al: Imaging advances in asthma. Expert Opinion on Medical
Diagnostics 2011, Vol. 5, No. 5 , Pages 453-465.
9. Siddiqui S, Gupta S, Haldar P, et al: Quantitative analysis of high resolution computed
tomography scans in severe asthma subphenotypes. Thorax 2010; 65:775–781.
10. De Blic J, Tillie-Leblond I, Emond S, et al: High-resolution computed tomography scan and
airway remodeling in children with severe asthma. J Allergy Clin Immunol 2005; 116:750–754.
11. Saglani S, Papaioannou G, Khoo L, et al: Can HRCT be used as a marker of airway
remodelling in children with difficult asthma? Respir Res 2006; 7:46.
12. Aysola RS, Hoffman EA, Gierada D, et al: Airway remodeling measured by multidetector CT is
increased in severe asthma and correlates with pathology. Chest 2008; 134:1183–1191.
13. Niimi A, Matsumoto H, Amitani R, et al: Effect of short-term treatment with inhaled
corticosteroid on airway wall thickening in asthma. Am J Med 2004;116:725-31.
14. Gupta S, Siddiqui S, Haldar P, et al: Qualitative analysis of high resolution CT scans in severe
asthma. Chest 2009; 136:1521–1528.
15. Ueda T, Nakano Y, Mishima M, et al: Clinical assessment of airway remodeling in asthma:
utility of computed tomography. Clin Rev Allergy Immunol 2004;27:45–58.
16. Busacker A, Newell JD, Jr., Keefe T, et al:A multivariate analysis of risk factors for the airtrapping asthmatic phenotype as measured by quantitative CT analysis. Chest. 2009; 135: 48-56.
17. Tunon-de-Lara JM, Laurent F, Giraud V, et al: Air trapping in mild and moderate asthma:
effect of inhaled corticosteroids. J Allergy Clin Immunol 2007; 119:583–590.
18. Mikos M, Grzanka P, Sladek K, et al: High-resolution computed tomography evaluation of
peripheral airways in asthma patients: comparison of focal and diffuse air trapping. Respiration.
2009;77(4):381–388.
19. Zeidler MR, Kleerup EC, Goldin JG, et al: Montelukast improves regional air-trapping due to
small airways obstruction in asthma. Eur Respir J. 2006; 27: 307-15.
20. Bumbacea D, Campbell D, Nguyen L, et al: Parameters associated with persistent airflow
obstruction in chronic severe asthma. Eur Respir J 2004; 24:122–128.
21. Takemura M, Niimi A, Minakuchi M, et al: Bronchial dilatation in asthma: relation to clinical
and sputum indices. Chest 2004; 125:1352–1358.
22. Leblond T and Tonnel AB: Allergic bronchopulmonary aspergillosis. Allergy ,2005: 60: 1004–
1013.
23. Ward S, Heyneman L, Lee MJ, et al: Accuracy of CT in the diagnosis of allergic
bronchopulmonary aspergillosis in asthmatic patients. AJR October 1999;173 ; 937-942.
24. Mitchell TA, Hamilos DL, Lynch DA, et al: Distribution and severity of bronchiectasis in
allergic bronchopulmonary aspergillosis (ABPA). J Asthma 2000;37:65 -72