1) Atiqur Rahman, a 16-year-old boy from Bogura, presented with increased cough, sputum production, breathlessness, and coughing up blood for several weeks. He had a long history of respiratory symptoms and was recently diagnosed with diabetes. 2) Examination found clubbing, crepitations on lung auscultation, and kyphosis. Investigations including sputum culture, sweat test, and CT scan confirmed cystic fibrosis with bilateral bronchiectasis and respiratory failure. 3) He was treated supportively in hospital and diagnosed with an exacerbation of cystic fibrosis-related lung disease and diabetes. Novel therapies that target the underlying CF gene defect are improving

1. 1
Welcome to Weekly Case
Presentation
DR HENA KHATUN
MD STUDENT ( Thesis Part )
On behalf of MU – II
NATIONAL INSTITUTE OF DISEASE OF THE CHEST AND
HOSPITAL

2. A Single Mutation Resulting
Multiple Diseases

3. Chief Complaints
Atiqur Rahman 16 years old boy
hailing from Bogura with the chief
complaints of
1) Increased cough and sputum production
for 1 month
2) Increased Breathlessness for 1 month
3) Coughing up of blood for 20 days
4) Fever for 10 days

4. History of present Illness
He has been suffering from recurrent attack of cough and
sputum production since his age of 3 years. And few years after
the onset of these illness the cough and sputum production
became persistent and present throughout the year. Sometimes
the severity of cough increases and the volume of sputum
production also increases with purulent character. In some
occasion it also becomes foul smelling. The days of increased
severity of illness is also associated with fever, malaise and
anorexia.

5. History of present Illness……..
•His amount of sputum varies between 30 ml to 250 ml per day.
•He is also suffering from breathlessness for the last 5 years on
moderate to severe exertion which has no diurnal or seasonal
variation. Not associated with wheeze,runny nose or nasal
blockade. Not aggravated by cold or dust exposure. Never
experienced paroxysmal nocturnal dyspnoea.
•Had no history of contact with tuberculosis patient.
•Gave no history of chest pain and swelling of ankle.

6. History of present Illness……..
•His bowel and bladder habit is normal.
•He is Normotensive and diagnosed as a case of diabetes
mellitus 17 months back and since then he is on insulin.

7. History of present Illness……..
•Cough , sputum production and breathlessness are increased
for the last one month. And for the first time he is suffering
from coughing up of blood for the last 20 days. Fever also
present for the last 10 days which is high grade intermittent in
nature subsides with taking paracetamol.
•Cough is occurring throughout the day and night . Sputum
became purulent with daily amount about 200 ml. And he is
breathless even at rest now.
•Initially haemoptysis was scanty but 3 days back about 500 ml
of blood is coughed up in 2 episodes.

8. History of present Illness………
•With these complaints he got admission in BMCH where
after initial management they referred him to NIDCH for
better treatment on 11th August of this year.

9. History of past illness
• Three times admission in hospital during the last 2
years for increased cough, sputum production and
dyspnoea.

10. Family History
• His elder brother had similar type of illness with
recurrent respiratory tract infection and died at the
age of 21 years. One of his sisters had also diabetes
and died at 20 years of age. Consanguinity is absent in
his parents.

11. Personal History
• He had to discontinue his study after class 8 due to his
chronic illness. He is non-smoker and non-alcoholic .

12. Socioeconomic Condition
• He came of a low socioeconomic status. His father is a
cultivator. They reside in a tin shed house and has
excess to safe drinking water and sanitation.

13. Drug History
For his illness he took several types of antibiotics and
other medication from local doctor but couldn't
mention the name.

14. General examination
• The patient is emaciated.
• Dyspnoic, excessory muscles of respiration are active , there is
excavation of suprasternal and supraclavicular fossa and intercostal
in drawing present.
• Well cooperative.
• Clubbing present in both toes and fingers.
• Anaemia, jaundice, cyanosis, oedema, dehydration, koilonychia and
leukonychia are absent
• No thyromegaly or lymphadenopathy
• JVP not raised
• No boney tenderness present

15. General examination…….
• Pulse 104/min
• BP 100/70 mm of mm Hg
• RR 28 breaths/min

16. General examination……

17. Respiratory System Examination
Inspection:
• Dyspnoic
• Kyphosis present
• Movement bilaterally symmetrical
Palpation:
• Trachea - central
• Apex beat – Left 5th ICS just medial to mid clavicular line
• Vocal fremitus – bilateral normal
• Chest expansion – bilateral symmetrical , total expansion 3 cm

18. Respiratory System Examination……..
Percussion note:
•Resonant bilaterally
•Upper border of liver dullness – 7th ICS in right mid clavicular
line
Auscultation :
•Breath sound – vesicular with prolonged expiration
•Added sound – coarse crepitation are present in all spaces
bilaterally along all three lines. Altered with coughing. Rhonchi
present.
•Vocal resonance – normal bilatarally

19. Kyphosis of the chest

20. • Other system examination reveals no abnormality.

21. Provisional Diagnosis
Exacerbation of Bilateral Bronchiectasis with Diabetes
Mellitus due to cystic fibrosis

22. Differential Diagnosis
• Acute Exacerbation of Childhood Asthma with
Bilateral Bronchiectasis with Diabetes Mellitus

23. Investigations
CBC:
• Haemoglobin 12.2 gm/dl
• Total WBC count – 18000/cmm
• N – 62%
• L – 26%
• M – 10%
• E – 02%
• ESR – 24
• Total platelet count – 225000/cmm

24. Investigations…..
• RBS – 366 mg/dl
• Blood urea – 35 mg/dl
• S. Creatinine – 0.9 mg/dl
• S. Bilirubin – 0.5mg/dl
• SGPT – 18u/L
• Sputum for AFB – negative
• Urine routine and microscopic exa.- sugar present +

25. Investigations…….
• USG of whole abdomen – Normal study
• Chest x-ray P/A view – normal study
• X-ray dorso-lumber spine - kyphosis
• CT scan of the chest – Bilateral bronchiectatic
changes in all lobes

26. 20/08/16

27. 30/08/16

28. 29/08/16

38. Spirometry with reversibility test( 3/9/16)
Actual Predicted %Predicted Actual %Predicted %Changed
FVC(L) 0.99 3.22 30 1.11 34 +12
FEV1(L) o.42 2.88 14 0.46 16 +11
FEV1/FVC 42 85 49 42 49 +0
FEF(L/sec) 1.25 6.31 19
FEF 25-
75%
0.18 3.42 5 0.23 6 +27

39. Six Minute Walk Test ( 3/9/16)
Variables Baseline At the end of Test After 5 min of rest
Pulse ( beats/min) 77 92 76
Spo2 (%) 87 75 86
RR (breaths/min) 28 32 28
Distance walked 1290 feet
Other observation:
SOB :Present
Chest pain : Absent
Taking rest during test : No.
Comment : Significant desaturation with mild limitation in walking distance.

40. ABG ( 3/9/16)
Variables Values
PH 7.39
PCO2 48.4
PO2 51
HCO3 28.6

41. Sputum for C/S
• Klebsiella Significant
• Sensitive to colistin, imipenem and
piperacillin/tazobactam
• Resistant to amikacin, levofloxacin, cefuroxime and
gentamycin.

42. Sweat test
• Sweat test for electrolytes – Sodium 165.60 mmol/L
Chloride 149.10 mmol/L
• Saccharin Test- Negative

43. Confirmatory Diagnosis
Exacerbation of Bilateral Bronchiectasis
With Diabetes Mellitus due to Cystic Fibrosis
with Type I Respiratory Failure.

44. Treatment given in Hospital
• Oxygen inhalation 4 to 5 litre per min
• Antibiotic – initially empirically and then changed according to
culture sensitivity
• Cap tranexamic acid
• Inj Amyinocaproic acid
• Nebulisation with bronchodilator
• Postural drainage of chest secretion and physiotherapy
• N-acetylcystine
• Insulin

49. Out come
• Haemoptysis is controlled
• Fever was subsided
• Cough and SOB reduced significantly
• Patient was able to do his daily self care without SOB.

50. Cystic Fibrosis
•Cystic Fibrosis is a progressive autosomal-recessive genetic ,
multi-system disease that affects lungs, sweat glands, gut
epithelium, pancreas, liver and reproductive tract and to which
there is no cure till today.
•It is the result of mutations affecting a gene on the long arm of
chromosome 7, which codes for a chloride channel known as
cystic fibrosis transmembrane conductance regulator(CFTR);
this influence salt and water movement across the cell
membrane.

51. Cystic Fibrosis…….
Medical and technological advancements have substantially
increased the life expectancy of CF patients, from an average
of eight years in 1974 to thirty in 2000 and thirty seven today
and some patients are even living into their 40s and beyond.

52. Cystic Fibrosis……..
• Behind this achievement there are efforts of so many
organizations world wide including Cystic Fibrosis
Foundation, USA ; the mission of the Foundation is to
cure cystic fibrosis and to provide all people with the
disease the opportunity to lead full, productive lives by
funding research and drug development, promoting
individualized treatment and ensuring access to high-
quality, specialized care

53. Lung Pathology
•The genetic defect causes increased resorption of sodium
and water from respiratory epithelium and dehydration of
the airway epithelium is thought to predispose to chronic
bacterial infection and ciliary dysfunction , leading to
bronchiectasis, progressive lung damage and ultimately
developed respiratory failure.

54. Cystic Fibrosis related Diabetes
•Hyperglycemia can occure due to progressive loss of the
pancreatic islets in CF.
•It can occur at any age but generally a problem in the second
and third decades of life.
•Ketoacidosis is rarely encountered.
•When blood glucose level is intermittently elevated and
glycosuria is not present, no treatment is necessary.
•If sustained glyscosuria develops, insulin treatment should be
instituted.
•Oral hypoglycemic agents are considered ineffective but may

55. Sweat Test
•The sweat test is considered the ‘’ gold standard’’ for the
diagnosis of CF.
•The acceptable procedure for diagnosis is called quantitative
iontophoresis.
•The method stimulate localized sweating on the forearm or
on the thigh using a chemical called pilocarpine.
•Sweat is then collected on filter paper or gauze or in
microbore tubing.
•The collected sweat is then analysed for chloride
concentration.

56. Procedure
•An area of skin on the arm will be washed and dried. Next,
two electrodes are attached with straps. One of these
contains a disc with pilocarpine gel, a medicine that makes
the sweat glands produce sweat. A weak electric current
pushes the medicine through the skin. After this is done, the
electrodes are removed and the skin is cleansed.

57. Step 1

58. Procedure ……..
• A special sweat collection device is then attached to the
clean skin surface in the area where the sweat glands were
stimulated. It’s taped to the skin to keep it from moving.
The sweat is collected for 30 minutes. The sweat that’s
collected turns blue when it comes into contact with blue
dye within the collector, making it visible to the technician.

59. Step 2

60. Interpretation of Sweat Test

61. Novel Therapy for Cystic Fibrosis
•Small molecules designed to correct the function of particular
CFTR defects are developed.
•One of the molecule is EVACAFTOR which is an oral
medication that is the first drug available that targeted the
underlying cause of CF- the defective CFTR protein.
•EVACAFTOR helps facilitate the opening of the chloride
channel on the cell surface to allow chloride and sodium to
move in and out of the cell.

62. Novel Therapy for Cystic Fibrosis…..
• In clinical trials , people with CF who took the drug
had improved lung function, reduced pulmonary
exacerbations, increased weight and improved quality
of life measures.

63. Thank
you for
Patience
Hearing!