An Interesting case of Treatment
resistant Asthma
Unit – III
Prof.Dr.V.Ushapadmini M.D.
Dr.Rajamahendran M.D.
Dr.Ranjith M.D.
Dr.V.R.Bhuvaneswari,Post graduate
CASE SUMMARY
Mrs.Chellamani,42 /F , agricultural labourer,
Chief complaints
Breathlessness on and off past 7 years, aggravated for past 1 year,
aggravated in early morning, aggravated in cold climate.
Cough with expectoration – past 1 year,more so past 2 weeks.
H/O blood stained sputum +
Chest pain-pleuritic type of pain right side past 2 weeks
H/o loss of weight +
N/o H/o evening rise of temperature or night sweats
No H/o Loss of appetite.
No H/o chest pain, palpitation, syncope.
No H/o swelling of legs or abdominal pain or distension.
Past history
Patient is a K/C/O bronchial asthma on treatment for past 7
years – with courses of short term steroids and Inhalers
Since the pt was poorly responding to treatment she was suspected to have
PTB and started on ATT in December 2016 But subjectively no
improvement
No H/O contact with TB or H/O HT,DM.CAD
Occupational history-Agricultural labourer with exposure to environmental
fungi
Personal history
Mixed diet consumer.
No specific addictions.
Family history
No similar complaints in family members.
On examination
Patient was conscious
Oriented
Afebrile
Ill built, emaciated
Pallor +
No clubbing
Vitals
Temperature-97.4 F
PR – 92/min
BP – 110/70 mm Hg
RR – 26/min
Respiratory system
Inspection
Trachea midline
chest is symmetrical
Movements equal on both sides
Palpation
Trachea in midline
Ap diameter – 18 cm
Transverse diameter – 30 cm
Chest expansion equal on both sides
VF – normal
No tactile fremitus
Percussion
All lung fields are resonant
Auscultation
Normal vescicular breath sounds
Coarse leathery crepitations heard in all lung fields
VR – normal
Other systems - normal
Provisional diagnosis
PT sequelae, Bronchiectasis .
HB- 8.5, TC- 8800, DC – P 58%, L20%,E-12%%, ESR – 35
MM in 1 hr, RBC – 2.6,PCV – 26%, Plt – 1.9 L.
Urea – 36, sugar – 128, creat – 1.2.
ECG – within normal limits.
Peripheral smear – normocytic hypochromic anemia.
Sputum AFB – negative. Sputum CB NAAT – negative
Sputum shows atypical organisms-Chlamydia/Mycoplasma
HIV - negative
. AEC – 126/cu.mm.
Patient was treated with i.v. Antibiotics, i.v. Bronchodilators and
Nebulisation.
There was no improvement.
Further evaluation done to find out the cause.
Final diagnosis- Allergic bronchopulmonary aspergillosis.
Expert opinion obtained and patient was started on T .
Itraconazole 200 mg bd, T.prednisolone – 30 mg OD
Patient symptoms improved significantly.
DISCUSSION
INTRODUCTION
ABPA - Idiopathic inflammatory disease of the lung – allergic
inflammatoryresponse to colonisation of airways by A.fumigatus
or other fungi.
Allergic bronchopulmonary mycosis-Identical clinical syndrome
is also seen with
C.albicans,Helminthosporium,alternaria,curvilaria,saccharomyc
es,stemphylium.
New entity – severe asthma with fungal sensitivity (SAFS).
Complicates 7 – 14 % of cases of chronic steroid dependent
asthma.
7 – 15 % of cases of cystic fibrosis.
common in 3 – 5 decades of life.
Familial cases – genetic factors play an important role.
Pathogenesis
Conidia colonize airways – germinate into somatic hyphae –
chronic allergic inflammatory response – tissue injury.
Gene mutations – CFTR, MHC Class II DR2/DR5-predispose,
DQ2 – protective. TLR 9, Chitotriosidase 1 exon mutation play a
role in pathogenesis.
Type I hypersensitivity – elevated total and A.fumigatus specific
IgE.
Type III hypersensitivity – A.fumigatus specific IgG antibodies,
circulating immune complexes.
Type IV hypersensitivity – immediate and delayed skin
sensitivity.
Helper T cells play a role in pathogenesis – increased airway T
helper cells,increased level of soluble interleukin 2 receptors in
the circulation.
Lymphocytes , eosiniphils, basophils contribute to local airway
injury.
Neutrophils play a role – IL 8,sputum neutrophilia, MMP levels.
Aspergillus derived antigens and proteases with antibody
binding capacity may amplify the inflammatory response.
Clinical features
Dyspnea
Wheezing
Poor asthma control
Cough – productive of thick, brown mucus plugs.
Malaise
Low grade fever
Occasionally hemoptysis.
History of recurrent asthma exacerbations with pneumonias.
Atopy
Clinical types
ABPA – seropositive-ABPA(S)
ABPA – central bronchiectasisABPA-(CB)
Severe asthma with fungal sensitivity
Patients with poorly controlled asthma with response to
antifungals – with some criteria of ABPA.
Milder allergic response
Lack of exaggerated IgG response
No radiographic abnormalities.
Differential diagnosis
Steroid dependent asthma without Chronic eosiniphilic pneumonia
ABPA Lymphoma
SAFS Idiopathic hypereosinophilic
COPD syndrome
Chronic necrotizing aspergillosis Auto immune disease
Tuberculosis Cocaine use
Parasitic infections Cystic fibrosis
Hypersensitivity pneumonitis
Churg-Strauss syndrome
Acute eosinophilic pneumonia
Diagnostic studies
BAL – eosinophilia, increased Aspergillus specific IgE and IgA
Bronchoscopy – mucoid impaction, bronchial brushing shows
aggregates of eosinophils, fungal hyphae and charcot laden
crystals.
Hyphae filled mucus plugs – pathognomonic of ABPA.
PFT – obstructive ventilatory defect. Stage V – restrictive defect.
Imaging
Typical manifestations – pulmonary infiltrates and Central
bronchiectasis.
Infiltrates are irregular and transient(1-6 weeks) .Fleeting infiltrates
Tramline shadows
Toothpaste shadows
Ring shadows
Local consolidation
Lobar collapse
Treatment
Goals – controlling symptoms, preventing
exacerbations,preserving normal lung function.
Systemic steroids are the mainstay.
Stage I, III – prednisone 0.5 – 1 mg/kg a day – 2 weeks
Followed by 0.5 mg/kg every other day – 6 – 8 wks.
Subsequently tapered by 5-10 mg every 2 weeks.
Low maintenance dose may be required (5 – 7.5 mg/day)
Cortico steroid therapy – relief of symptoms, >35% decrease in
serum IgE., reduction in peripheral blood eosinophils, resolution
of pulmonary infiltrates.
IgE levels –monitored every 2 months.
Escalation of steroid therapy – if IgE levels rise more than 100%.
Antifungals – Itraconazole 200 mg twice daily for 16 weeks.
Reduction in steroid dosage
Decreased IgE levels.
Greater resolution of pulmonary infiltrates.
Gains in exercise tolerance or pulmonary function.
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