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.

THANK YOU