2. History Asthma : derived from the Greek aazein, meaning "sharp breath." The word first appears in Homer's Iliad. In 450 BC. Hippocrates: more likely to occur in tailors, anglers, and metalworkers. Six centuries later, Galen: caused by partial or complete bronchial obstruction. 1190 AD, Moses Maimonides: wrote a treatise on asthma, describing its prevention, diagnosis, and treatment 17th century, Bernardino Ramazzini: connection between asthma and organic dust. 1901: The use of bronchodilators started. 1960s: inflammatory component of asthma was recognized and anti-inflammatory medications were added to the regimens.
4. ASTHMA Chronic inflammatory condition of the airways characterized by; - airflow limitation (reversible with treatment) - airway hyper-responsivenessto a wide range stimuli - inflammation of the bronchi In chronic asthma, inflammation maybe accompanied by irreversible airflow limitation Symptoms are cough, wheeze, chest tightness, and shortness of breathwhich often worse at night
5. Simple Definition A reversible chronic inflammatory airway disease which is characterized by bronchial hyper-responsiveness of the airways to various stimuli, leading to widespread bronchoconstriction, airflow limitation and inflammation of the bronchi causing symptoms of cough, wheeze, chest tightness and dyspnoea.
6. Epidemiology Majority of patients(87.3%) had mild asthma; 9.9% had moderate asthma and 2.7% had severe asthma Among severe asthmatics, only 19.4% were on inhaled corticosteroids Common disease with unacceptably high morbidity and mortality Commonly underdiagnosed and undertreated Only 36.1% of adult asthmatics ever had their peak flow measured Higher prevalence in rural (4.5%) than in urban areas (4%),lower educational status(5.6%) and lower income
8. EPIDEMIOLOGY The prevalence of asthma has increased 61% over the last two decades. Asthma is the leading chronic illness among children. Asthma results in 10 million lost school days and 3 million lost work days. Deaths from asthma have increased by 31% since 1980.
9. Classification Extrinsic – implying a definite external cause more frequently in atopic inviduals (atopic – individual which tends to develop hypersensitivity by contact with allergens) often starts in childhood - accompanied by eczema Intrinsic/cryptogenic – no causative agent can be identified starts in middle age
10. Types of Asthma According to the severity: helpful for treatment and management.
11. Types of Asthma According to pathophysiology Allergic asthma Occupational (allergic) ABPA (allergic) Intrinsic (Non-Allergic) Exercise-induced Steroid-resistant
12. Pathogenesis Complex, not fully understood numbers of cells, mediators, nerves, and vascular leakage -activated by expose to allergens or several mechanism Inflammation Eosinophils, T-lymphocytes, macrophages and mast cell Remodeling Deposition of repair collagens and matrix proteins-damage Loss of ciliated columnar cells- metaplasia – increase no of secreting goblet cells
13. Pathologic features of asthma Inflammatory cell infiltration of the airways Increased thickness of the bronchial smooth muscle Partial or full loss of the respiratory epithelium Subepithelialfibrosis Hypertrophy and hyperplasia of the submucosal glands and goblet cells Partial or full occlusion of the airway lumen by mucous plugs Enlarged mucous glands and blood vessels
14. Pathophysiology Smooth muscle contraction Thickening of airway –cellular infiltration and inflammation Excessive secrection of mucus Genetic factor Cytokine gene complex (chromosome 5)-IL-4 gene cluster control IL-3, IL-4 , IL-5 and IL-13 Environment factor Childhood expose irritants or childhood infection
15. Pathophysiology Extrinsic asthma: Atopic/allergic, occupational, allergic bronchopulmoaryaspergillosis. Atopic or allergic Dust, pollens, animal dander, food etc. Family history of atopy. ↑ serum IgE. Skin test with Ag wheal, flare ( Classical IgE mediated response) Exposure of pre-sensitised mast cells to the Ag stimulates chemical mediators from these cells. Type 1 hypersensitivity.
16. 1.Early phase Inhaled Antigen Sensitised mast cells on the mucosal surface mediator release. Histamine bronchoconstriction, increased vascular permeability. prostaglandin D 2 bronchoconstriction, vasodilatation. Leucotriene C4,D4, E4 Increased vascular permeability, mucus secretion and bronchoconstriction. Direct subepithelialparasympathetic stimulation bronchoconstriction.
17. 2.Late phase starts 4 to 8 hours later Mast cell release additional cytokine Influx of leukocytes(neutrophil,eosinophil) Eosinophils are particularly important- exert a variety of effect
23. Aetiology and triggers Occupational sensitizers isocyanates(from industrial coating, spray painting) colophony perfumes(electronic industries) Drugs NSAIDS B-blocker(B1 adrenergic blocker drug such as atenolol is avoided to treat HPT and angina in asthmatic pt Cold air Exercise exercise-induced wheeze is driven by histamin and leukotrienes which are release from mast cells when epithelial lining fluid of the bronchi become hyperosmolar owing to drying and cooling during exercise Emotion
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28. History Presenting symptoms: Cough ± sputum - time: become worse at night - duration: chronic / acute - associated with wheezing - fever? URTI Wheeze - max during expiration and accompanied by prolonged expiration
29. Cough History 1.Ask specifically about the symptoms: -Cough?how is the cough? more severe at night or on day? associated symptoms like dyspnea & wheezing? how long is the cough? Recurrent?Any previous similar episode? Aggravated factor?like cough become severe after exercise?or the cough is initiated after exercise?
30. Cough History 2.If the cough is associated with dyspnea and wheezingis it relieved by bronchodilator? 3.Ask for any precipatating factors -whether the symptoms(cough,dyspnea,wheezing) started after exposure to weather changes, dust, exercise, infection or drugs? 4.Is there any pets,carpet or feather pillow in home?(easily trapped dust and the dust or animal fur will cause exacerbation of asthma)
31. Dyspnoea History Dyspnoea - onset: after exercise? cold? dust? animal fur? emotion? - severity and pattern: varies from day to day or from hour to hour - no chest pain
32. History Clinical features Recurrent episodes of wheezing,chesttightness,breathlessness and cough Precipitants- cold,allergen,pollutant,viralurti Exercise tolerance Disturbed sleep Other atopic disease Home-Pet?Carpet? Occupation
36. History Past medical history: Experienced asthma attack before Taking any medications: NSAIDs / β-blocker / aspirin (non atopic asthma) Family history: Has family history of asthma
37. History Social history: Occupation: expose to fumes/organic/chemical dust House: near to factory? Pets? Dust? Carpet? Feather pillow? Smoking in any family members
38. known asthmatic When he was diagnosed with asthma? How the asthma was diagnosed? Who diagnosed it? Whether he is on prophylaxis? What type of prophylaxis? How he get the drugs and how many dosage of the drugs? Whether he know how to deliver the drugs properly? How is his compliance to drugs?
39. Physical examination General inspection: - tachypnoeic, sign of respiratory distress, effort of breathing, cyanosis (life-threatening) Inspection: - fingers: tar staining - pulse rate: tachycardia and pulsusparadoxus, bradycardia (life-threatening) - used of accessory muscles or recession - wheezing
40. Chest Percussion: - may be hyperresonance / normal Auscultation: - breath sound: vesicular - ronchi in expiratory phase, may be both in severe asthma - prolonged expiratory phase -vocal resonance decrease / normal Inspection: - shape: hyperinflated in severe asthma - movement of chest/silent chest (life-threatening) - chest deformity: - recession: Palpation: - chest expension may be reduce (hyperinflated)/ normal - apex beat: may be displaced -vocal fremitus: decrease
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43. Severe attack – inability to complete sentences, pulse >110bpm, RP>25/min, PEF 33-50%
46. At the onset of an attack, patients experience a sense of constriction in the chest, often with a nonproductive cough.
47. Respiration becomes audibly harsh; wheezing in both phases of respiration becomes prominent; expiration becomes prolonged; and patients frequently have tachypnea, tachycardia, and mild systolic hypertension.
71. Specific investigation Specific: - respiratory function test: 1. peak expiratory flow 2. spirometry - exercise tests -histamine/methacholine bronchial provocation test - trial of corticosteroids
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73. An improvement of 15% or more (as measured on the peak flow meter) is diagnostic of asthma.
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75. Peak expiratory flow rate Simple and cheap Subject take full inspiration then blow out forcefully into peak flow meter. Best used to monitor progression of the asthma and its treatment. To access possible occupational asthma PEFR value varies with sex, age and height.
76. Peak Expiratory Flow Rate (PEFR) The maximum rate of air breathed out as hard as possible through a measuring device called a peak flow meter, (after a full breath taken in). Reading is measured in litres/minute (l/min). Take 3 readings and choose the best Reading < 80% - presense of obstruction, but not diagnostic of asthma
77. Require to take a series of reading - on waking up - prior taking bronchodilator - after taking bronchodilator (before sleep)
78. PEF measurements During periods of well-being: provides measurement of the patients best PEF value which will provide the target for the doctor and the patient to aim for.Twice daily measurements before any inhaled bronchodilator tx will determine the diurnal variability of airway calibre.Good control of asthma means PEF variability is maintained at less than 10%. During symptomatic episodes: During an attack of asthma PEF fairly accurately measures the degree of bronchospasm.A PEF of less than 50% of normal or best suggests a very severe attack and a PEF of less than 30% suggests a life-threatening attack
99. Chest X-ray Showed lung hyperinflation. Not diagnostic of asthma Useful to rule out other causes eg. Pneumothorax ----------------------------------------------- Hyperinflation and increased bronchovascular markings
100. Allergies & Atophy Allergen Provocation Test In suspected occupational asthma and food-allergy related asthma Skin-Prick Test To identify allergens A drop of allergen is placed on skin , site is marked and pricked with needle, measured any weals
113. reducing peak flow rates). Self management plan for selected, motivated patients or parents. The danger of non prescribed self medication including certain traditional medicines. Natureof asthma Preventive measures/avoidance of triggers Drugs used and their side-effects Proper use of inhaled drugs Proper use of peak flow meter Knowledge of the difference between relieving and preventive medications
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115. Aspirin and nonsteroidal anti-inflammatory drugs if known to precipitate asthma, these drugs should be avoided.
116. Allergens e.g. house dust mites, domestic pets, pollen should be avoided whenever possible.
119. Day to day triggers such as exercise and cold air. It is preferable to adjust treatment if avoidance imposes inappropriate restrictions on lifestyle.
176. 1. Assess severe attack Severe attack: a) Unable to complete sentences b) RR>25/min c) PR>110 bpm d) PEF< 50% of predicted or best Life-threatening attack: a) PEF<33% of predicted or best b) Silent chest, cyanosis, feeble respiratory effort c) Bradycardia/ hypotension d) Exhaustion, confusion, or coma e) ABG : normal/high PaCO2>5kPa (36mmHg) PaO2< 8kPa (60mmHg) low pH, e.g. <7.35
215. Oral corticosteroids: necessary for severe asthma in pregnancy but usually only for short periods.Increased risk of cleft palate in animals given huge doses of oral steroids
226. In HSB respiratory distress upon admission CXR: mediastinal mass on right perihilar region multiple cannon ball lesions in both lung fields, so CT thorax, abdomen and pelvis done Huge anterior mediastinalmass encasing great vessels with lung metastasis and lymphadenopathy. Referred to UMMC for possibility of malignancy.
227. Past history Asthma since age of 7 years not on regular follow-up or treatment/prophylaxis mild infrequent diurnal symptoms no interference with general activity or school attendance. acute exacerbation: twice a year and precipitated mainly by coldness. No hospital admission
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230. Genitalia: pubic hair stage 3, penile length 7.5cm, testes 2 ml each. Breast tissue: gynaecomastia.
241. LH 11 mu/ml (H) (<0.1-6) FSH 33 mu/ml(H) ( 1.2-2.5) Estradiol <37 pmol/l (0-198) Testosterone 2.3 nmol/l (L) (8.4-28.7) DHEAS 0.5 umol/l (L) (2.2-15.2) Karyotyping: 47 XXY, how many cells? Any evidence of mosaic Klinefelter? (waiting formal report).
242. diagnosis Mediastinal germ cell tumor with bilateral lung metastasis and pseudoprecocious puberty. Klinefelter syndrome.
243. Management and progress Respiratory support, required BiPAP . Required neb Salbutamol 4 hourly. Had spikes of fever, covered with Erythromycin and Ceftriaxone. After 4 days in PICU transferred to P6. Started chemotherapy(UKCCSG). Had NNF covered with piptazocin then imipenem and later on Ampho-B.
246. Klinefelter syndrome In 1942 Klinefelter et al published a paper on 9 men with large breasts, minimal sexual and body hair, small testes and inability to produce sperms. It is the most common syndrome assoc with male hypogonadism and infertility. Classically 47XXY, but many variants like 48 XXXY, 48XXYY,49XXXXY,49XXXYY,50XXXXYY. It is due to meiotic non-disjunction. mosaic patients may be fertile .
247. Features Hypogonadism (small testes and azoospermia-hyalinzation and fibrosis of seminiferous tubules). Gynaecomestia in late puberty (30-50%) due to increase estradiol/testosterone ratio. Psychosocial problems. Elevated urinary gonadotrophins. Mental retardation is affected by number of X chromosomes (decreased IQ 15 points for each X chromosome) [most males with 47XXY have normal intellegence, 70% have minor developmental and learning disability]
248. Other features: Pescavus, genuvalgus, fifth finger clinodactily. Taurodontism (prominent molar teeth): 40% in Klinefelter, 1% in general population. Radio-ulnarsynostosis---- 49XXXXY.
251. Mortality 40% of conceptions with Klinefelter survive fetal period. Mortality is not significantly higher in healthy individuals.
252. Prevalence: in USA 1:500-1000 Race: no race difference. Age: it goes undetected in most affected males until adulthood. the common indication for karyotyping is hypogonadism and infertility.
253. investigations Mid-puberty: increase FSH and LH, decrease testosterone. Increase estradiol/testosterone ratio-----gynaecomastia 80%. Cortisol should be checked (47% have low cortisol). Decrease osteocalcin---- bone resorption. Coagulation profile because of increased risk of DVT and pulm embolism. Karyotyping:47 XXY 80-90 % - 10% mosaic.
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255. Primary mediastinal germ cell tumors Comprise only 1-3% of germ cell tumors. Overall teratoma is the most common variant, seminomais the most common malignant variant. Malignant variants are uncommon and more in males. Benign variants are equally disributed among males and females. Testicular examination, U/S and CT are mandatory to rule out testicular primary cancer.
256. Serum markers Alpha-fetoprotein: indicates malignant non-seminomatous type. BhCG: suggests trophoblastic component. Malignant non-seminomatous and mixed GCTs carry worse prognosis than other GCTs.
257. Association of M- GCTs with Klinefelter syndrome Klinefelter syndrome is present in 20% of patients with M-GCT. The incidence of M-GCT is 50 fold increased in patients with Klinefelter syndrome. M-GCT mask the usual clinical signs of Klinefelter syndrome by inducing puberty by BhCG.
258. Comparison of GCT between KS and general population Klinefelter syndrome: All contain non-seminominatous elements Present at younger age (mean 17 years) Precocious puberty is seen more often. Almost exclusively extragonadal. General population: Pure seminoma is the most common malignant variant. Older age at presentation (mean 29 years) Precocious puberty is less often. Only 2-5% extragonadal.