Respiratory Flashcards
(149 cards)
1
Q
Define Asthma
A
A chronic inflammatory disease characterised by intermittent airway obstruction and hypersensitivity. It is a T1+4 mediated hypersensitivity reaction with bronchial constriction and increased mucus production.
2
Q
List RFs for asthma (3 STRONG 3 WEAK)
A
Strong = FHx, Allergen exposure, Atopy Weak = Obesity, GORD, Nasal Polyposis
3
Q
List signs and symptoms of asthma
A
RFs Expiratory wheeze URTI Cough (often @ night) Nasal polyposis Dyspnoea
4
Q
Name 5 investigations into asthma
A
FEV1/FVC = <80%; or >12% improvement after SABA
FEV1 = <80%
If still suspect asthma due to symptoms but no positive investigations proceed with PFTs after Methacholine/Histamine challenge
CXR = possible hyperexpansion
Skin spot test to allergen = <3cm reaction
Immunoassay for specific allergen = +ve
PEFR = helps determine severity of exacerbations
5
Q
Briefly outline the 6 asthma treatment steps
A
- SABA + low dose ICS
- SABA + low dose ICS +/- LTRA (montelukast)
- SABA + med dose ICS
- LABA + med dose ICS
- LABA + high dose ICS
- Oral CS + LABA
Theophylline and amophylline can be added throughout
Omalizumab can be used = immunomodulator
6
Q
Define ABPA
A
Hypersensitivity reaction to aspergillosis, which is inhaled into the alveoli and colonises the bronchi, in an otherwise immunocompetent person
7
Q
List 6 RFs for (4 strong 2 weak)
A
Strong = Atopy, Asthma, HLA DR2/5, CF Weak = CFTR mutation, Surfactant mutation
8
Q
What are the signs and symptoms of ABPA?
A
Coughing, mucus plugging, pleuritic chest pain, wheezing, fever, typically YA, asthma/atopy
Late = cyanosis, clubbing, WL
9
Q
List investigations into ABPA
A
Aspergillosis Fumigatis skin testing - +ve wheele and flare
Serum IgE and IgG - H
CXR - upper and middle lobe infiltrates
FBC - Eosinophilia
Sputum culture - +ve/-ve
CT - CxR findings + possible bronchiectasis, mucus plugging, impaction,peri-bronchial thickening
10
Q
Define bronchiectasis
A
Permanent dilation of the bronchi as a result of destruction to the smooth muscle and elastic components. It is often a consequence of recurrent severe infections.
11
Q
Name some causes/RFs for bronchiectasis
A
V - N I - ABPA, TB, severe childhood infections T - N A - UC, Crohns, RhA M - N I - >50% idiopathic N - Bronchial carcinoma C - CF, Marfans, Ehlers-Danlos D - N E - N
12
Q
List 7 symptoms of bronchiectasis
A
Recurrent infections Sputum plugging Haemoptysis, Rhinosinusitis Fever Cough Dyspnoea Wheezing Crackles and high pitched squeaks WL Other - pleuritic pain + clubbing
13
Q
List the main investigations for bronchiectasis
A
CxR - MAY BE NORMAL. May see evidence of dilated bronchi, tubular opacities, obscured hemi-diaphragm
HIGH RES CT - Gold standard - same as CxR, but also thickened bronchi, tree in bud pattern
Sputum culture - if concomitant infection
FBC - eosinophilia (ABPA) / Neutrophilia (infection)
14
Q
What treatments are available for bronchiectasis?
A
All dependent on severity/exacerbations
1st - Exercise, diet mo, airway clearance therapy
2nd - bronchodilator SABA/ipatropium
3rd - inhaled macrolide (azithromycin) reduces sputum, infection
4th - prophylactic abx
5th - Surgery - resection of bronchiectic tissue
Vent fail- NIV and O2
15
Q
List 3 complications of bronchiectasis
A
Massive haemoptysis - lie pt on side of bleeding
Resp failure - airway protection and O2 + NIV
Cor pulmonale - due to increased RV strain and PHTN
16
Q
Define CAP
A
Pneumonia acquired outside of hospital. It is a LRTI characterised by cough, fever, dyspnoea and alveolar infiltration.
17
Q
List 2 common causes if CAP
A
S. Pneumonia = 35%
H. Influenza
18
Q
List 3 atypical causes of CAP
A
M. Pneumonia, C. Pneumonia, L, pneumophilia, P jirevocii
19
Q
List RFs for CAP
A
Strong = Residence in healthcare setting, COPD, elderly <65, smoking, contact with children, poor oral hygiene Weak = DM, CKD, CLD
20
Q
List findings + symptoms of pneumonia
A
Symptoms = productive cough, fever, chills, dyspnoea, pleuritic chest pain. Other = myalgia, arthralgia, confusion (elderly)
Signs = dull percussion, asymmetrical breath sounds, bronchial breathing, fine end insp crackles, increased vocal resonance, pleural rubs.
21
Q
Investigations into CAP
A
CxR - infiltrations/consolidation FBC - WCC H Sputum/blood culture CRP - H ABG - L O2 poss U+E - Normal Reverse PCR - if suspect viral origin
22
Q
Name 2 simple Rx steps in CAP
A
Tailor Rx to sputum culture
Macrolides = First line = azithromycin/clarithromycin
2nd = Ceftriaxone + azith/clarith OR amoxicillin and azith/clarith
Minimum 5 days, stopped 48hrs after symptoms gone
23
Q
Define COPD
A
Airflow limitation that it treatable but not fully reversible. It encompasses both bronchitis and emphysema.
Bronchitis = ciliary dysfunction and increased goblet cell numbers resulting in increased mucus production and failed clearance
Emphysema = chronic hypoxia induces SM thickening, elastin breakdown and a loss of alveolar integrity
24
Q
List RFs for COPD
A
Tobacco smoking - 40-70% causes A-1-antitrypsin def - leads to imbalance of proteinases and antiproteinases Male Dec Socio White Age >65yo Air pollution
25
List the COPD signs and symptoms
Signs - tracheal tug, hyperexpansion, increased resonance, coarse crackles, accessory muscle use, distant breath sounds, asterixis, distended neck veins, JVP, cyanosis, loud P2, clubbing, tachypnoea, splenomegaly
Symptoms - SOB, dyspnoea, dec exercise, cough, inc mucus, wheezing and stridor,
26
List the main investigations into COPD
```
FEV1/FVC - <70%
Pulse oximetry - Dec sats
ABG - PaCo2 >6.6kpa. PaO2 < 7.9kpa
ECG - RVH / arrthymia / ischaemia
FBC - WCC H
Consider sputum sample if evidence infection
CT chest - hyperinflation
```
27
What are the 5 main steps in COPD Rx?
1. SABA / tiotropium bromide
2. Oral CS transition to -> ICS
3. SABA - LABA
4. Phosphodiesterase-4-inhibitor (ROFLUMILAST) // or Xanthine derivative (aminohylline/theophylline)
5. Lung transplant
ALL NEED - education, smoking cessation, vaccination, potential O2 supplementation
28
List the complications of COPD.
Cor pulmonale (PHTN), recurrent pneumonia, pneumothorax, resp failure during infection, anaemia, polycythaemia, depression
29
Define pneumoconiosis
A group of interstitial lung diseases resulting from inhalation of mineral or metal particles. Includes silicosis, chron beryllium and black lung (coal workers) disease
30
List the RFs for pneumoconiosis
Strong - tobacco, occupational, cumulative exposure
31
List the signs and symptoms of pneumoconiosis
MAIN 3 = dyspnoea on exertion, cough (dry), normal chest exam
Others = clubbing, dull percussion (very fibrotic), cyanosis, WL (late stage), barrel chest, crackles (early on)
```
RF = often occurs in these individuals - oedema, weight gain, HTN
TB = often complicates this disease - fever, night sweats, WL, haemoptysis
```
32
List some investigations into a possible pneumoconiosis sufferer.
CxR - APICAL fibrosis - appears as rounded opacities/honeycomb appearance
Spirometry = can be restrictive, obstructive or normal
Beryllium proliferation test - WC +ve response
Bronchoalveolar lavage - granulomas seen in beryllium
O2 sats - L
ABG - L pO2
CT - apical fibrosis (if cxr not conclusive)
33
What is a pneumothorax?
Whereby air gains access to and accumulates in the pleural space. Results in compression atelectasis and inability to oxygenate adequately.
34
What are the 5 subtypes/classes of pneumothorax?
1* spon = occurs spontaneously in an individual with no underlying lung disease
2* spon = occurs spontaneously in an individual with underlying lung disease
Catamenial = occurs secondary to thoracic endometriosis
Traumatic = occurs secondary to trauma
Tension = can complicate ANY form of pneumothorax = MEDICAL EMERGENCY AND IMMEDIATE MCL 2ND ICS DECOMPRESSION WITH 14 GAUGE CATHETER
35
List the signs and symptoms of a pneumothorax?
SO chest pain, SO dyspnoea, absent breath sounds, hyper-resonance, increased expansion ipsilaterally, tracheal deviation if tension.
36
Name a few RFs for a pneumothorax?
```
Male
Slender
Tall
Smoking
FHx
Age <40
Trauma
Secondary diseases - TB COPD CF ASTHMA MARFANS
```
37
List relevant investigations for a pneumothorax?
CxR - visualisation of pleural line and reduced area of vascularity/darkness
CT - hyperexpansion and underlying disease
Bronchoscopy - useful if obstruction/tumour caused
USS - used in emergency setting if unclear.
38
What are the Rxs of a pneumothorax?
TENSION = MEDICAL EMERGENCY AND IMMEDIATE DECOMPRESSION WITH A STANDARD 14G CATHETER
Rx for 1* 2* and catamenial = same. 2* more likely requires hospitalisation due to underlying disease.
If small (<2cm) then supportive + O2 + observation
If large (>2cm) then:
1. Decompression using chest tube or small bore catheter
2. If fails -> same but using chest tube thoracostomy
3. If fails -> VATS with stapling or talc pleuradhesis
TRAUMATIC = fluid (blood) aspiration then thoracostomy then thoracotomy
39
What are the complications of a pneumothorax?
Re-expansion pulmonary oedema if >72hrs before presentation/too fast air evacuation
ARDS - from talc pleuradhesis
1* = 30-50% reoccurrence. Even higher risk if 2*.
5% risk with stapling = more definitive
40
What is a PE?
The consequence of a thrombus formation in the distal veins which embolises to the pulmonary vasculature.
41
What are the symptoms of a PE?
Tachypnoea, SO pleuritic pain, haemoptysis, syncope, dyspnoea, cyanosis, hypotension, sternal heave, cough, DVT signs, tachycardia, JVP, distended neck veins, LOUD s2 - PHTN
42
Investigations for PE?
ECG - atrial arrhythmia, RBBB, S1Q3T3 = st changes in v1, inferior Q wave in v3, T wave inversion v3
CxR - band atelectasis, prominent pulmonary artery, oligaemia, elevation of hemidiaphragm
V/Q - areas of ventilation w/o perfusion
CT pulmonary angiography - reduced BF
Wells score +1 = suggestive
D-dimer - H in PE
Thrombophilia, TTE, TOE
43
Rx for a PE
O2 + mechanical vent (red T2RF) + IV fluids if hypo
NO BLEEDING RISK = alteplase 100mg iv 2 hrs
BLEEDING RISK = thrombectomy +/- IVC filter
IV anticoagulation after procedure -> to warfarin/enoxaparin/dalteparin
44
Complications of PE
RV failure -> MI
Pulmonary infarction
Acute bleed from heparin ass thrombocytopenia - GIVE FFP AND VIT K
45
List the signs and symptoms of TB
Cough (dry), haemoptysis, fever, WL, night-sweats, dyspnoea, malaise, apical crackles (end insp), asymptomatic, erythema nodosum, clubbing, psych symptoms, pleuritic pain, cervical lymphadenopathy (rare),
46
List relevant investigations for TB
CxR - apical opacifications +/- cavitation. May be normal
Sputum AFB smear - visualisation of AFB
Sputum culture - although it takes a while to grow/may not = useful in order to test abx susceptibility
IGRA/ellispot = WBC release of IG on exposure to TB
NAAT - nucleic acid amplification testing - evidence TB
Mantoux testing/tuberculin skin testing - >5mm reaction
HIV testing
47
Define asbestosis
Asbestosis is diffuse interstitial fibrosis of the lung as a consequence of exposure to asbestos fibres. Pleural abnormalities, which are also caused by the inhalation of asbestos fibres, include plaques that may or may not be calcified, diffuse pleural thickening, benign pleural effusions or rounded atelectasis. These pleural abnormalities may occur either in concordance with or in the absence of parenchymal fibrosis.
Disease onset occurs ≥10 years following the initial exposure to asbestos.
Patients may be asymptomatic or have progressive shortness of breath.
CXR is the preferred initial test.
There is no definitive treatment.
Cigarette smoking cessation is important to reduce risk of lung cancer.
Prognosis is related to extent of fibrosis noted at diagnosis and past cumulative exposure to asbestos.
48
Epidemiology of asbestosis
Asbestos use in developed countries has markedly decreased (its use is banned in many European countries). Currently, the risk of exposure in these regions is greatest among construction and/or maintenance workers who work with or around previously installed asbestos.
In 2016 in the UK, 1050 new cases of asbestosis were assessed under the Industrial Injuries and Disablement Benefit scheme; around 1-2% of these cases were female.
49
Aetiology of asbestosis
When asbestos fibres are inhaled, they deposit at alveolar duct bifurcations and cause an alveolar macrophage alveolitis. These activated macrophages release cytokines, such as tumour necrosis factor and interleukin-1beta and oxidant species, which initiate a process of fibrosis.
The cause of asbestosis and asbestos-related pleural changes is the inhalation of asbestos fibres. Asbestos is a fibrous silicate, which exists as a naturally occurring mineral. Chrysotile is the primary asbestos mined. The other 5 types of asbestos that are mined commercially are known as amphiboles and include actinolite, amosite, anthophyllite, crocidolite, and tremolite.
Airborne asbestos particles <10 microns can be inhaled. The more asbestos inhaled the greater the risk of developing asbestosis. The minimum amount required to cause asbestosis is unknown, but a level of 10 fibre/mL-years is a reasonable estimate.
50
RFs for asbestosis
STRONG
Cumulative dose of inhaled asbestos
WEAK
Cigarette smoking
51
Sx of asbestosis
COMMON
Dyspnoea on exertion
Cough
Crackles
UNCOMMON
Indirect exposure
Chest pain
Clubbing
52
Ix for asbestosis
CXR (PA and lateral) - lower zone linear interstitial fibrosis; progressively involves the entire lung; pleural thickening
PFTs restrictive - Restrictive: reduced FVC, normal FEV1/FVC ratio, reduced slow vital capacity (SVC), reduced TLC, reduced lung diffusion capacity testing (DLCO). - restrictive changes; may have obstructive picture (especially if history of asbestos exposure and smoking)
53
Rx of asbestosis
The increased risk of lung cancer in non-smoking asbestos workers is 5.2 - SMOKING CESSATION
Supportive - Antibiotics should be given if there is evidence of infection, such as change in sputum production, fever and increasing dyspnoea.
Patients with evidence of obstructive airways disease should receive appropriate bronchodilator therapy
Pulmonary rehabilitation is designed to reduce symptoms and optimise functional status. It involves exercise training, education, nutritional intervention, and psychosocial support. It is recommended for patients with exertional dyspnoea to improve exercise tolerance.
Oxygen therapy improves exercise tolerance and reduces the risk of developing pulmonary hypertension and cor pulmonale.
A patient may develop diffuse pleural thickening of sufficient extent that pleural decortications should be considered. However, this is very rare and pleural thickening does not usually require treatment.
Patients with end-stage respiratory failure (PaO2 <60 mmHg despite oxygen therapy) due to parenchymal disease are potential candidates for lung transplants.
54
Prognosis of asbestosis
Asbestosis
Prognosis is related to extent of fibrosis noted at diagnosis and past cumulative exposure to asbestos. Many patients with asbestosis will not progress and will go on to die from other conditions.
Pleural disease
A patient with only pleural changes is unlikely to develop asbestosis, as pleural changes occur after a long latency from first exposure and if asbestosis were to occur it is likely to have done so already.
55
Complications of asbestosis
```
Cor pulmonale
Lung cancer
Mesothelioma
Colon cancer
Laryngeal cancer
```
56
A 67-year-old retired construction worker has shortness of breath with activity that has been gradually getting worse, and a chronic cough. He denies chest pain. He has a 45-pack-year smoking history, but stopped smoking aged 50 years. There is no family history of lung disease. He does not take any respiratory medicine on a regular basis. With colds he has noticed wheezing and his doctor once prescribed an inhaler.
asbestosis
Rarely, a patient may present with an acute pleural effusion or pleurisy with fever and chest pain, which may last weeks to months. Over time, these patients are likely to develop diffuse pleural thickening.
57
A 55-year-old factory maintenance worker falls at work. A CXR is performed to evaluate the patient for a possible broken rib. Bilateral pleural thickening is seen on CXR. Further history indicates he is very active without any respiratory symptoms. He smokes 20 cigarettes a day. There is no family history of lung disease. He does not take any respiratory medicine.
asbestosis
Rarely, a patient may present with an acute pleural effusion or pleurisy with fever and chest pain, which may last weeks to months. Over time, these patients are likely to develop diffuse pleural thickening.
58
Define mesothelioma
Malignant mesothelioma is an aggressive epithelial neoplasm arising from the lining of the lung, abdomen, pericardium, or tunica vaginalis. It is one of the few cancers related directly to an environmental exposure; asbestos is the chief causative agent.
Malignant pleural mesothelioma accounts for most malignant mesotheliomas; it is a rare malignancy with an annual incidence in the US of 3200.
Largely caused by exposure to asbestos, with a 20- to 40-year latency period between exposure and development of malignancy; consequently the typical patient is in the sixth to ninth decade of life.
Most patients present with shortness of breath and chest pain, which on investigation is often found to be associated with unilateral pleural effusion and pleural thickening.
Despite advances in treatment, malignant pleural mesothelioma remains a highly lethal malignancy with few long-term survivors.
59
Epidemiology of mesothelioma
The disease is more common in men and white people, and typically occurs in older adults (sixth to ninth decade of life).
60
Aetiology of mesothelioma
Exposure to asbestos is the principal risk factor; about 80% of patients have a history of asbestos exposure.
61
RFs for mesothelioma
STRONG
Asbestos exposure
60-85
```
WEAK
Asbestos exposure during home maintenance and renovation
Male sex
Radiation exposure
Genetic predisposition
Siman virus 40
```
62
Sx of mesothelioma
```
COMMON
SOB
Reduced breath sounds - Usually a result of pleural effusion, trapped lung, or bronchial obstruction.
Dullness to percussion - Suggests presence of a pleural effusion on the affected side.
Male
Chest pain
Cough
Constitutional symptoms
```
UNCOMMON
Abdominal distension - Uncommon, but can occur as a consequence of extension to the abdominal cavity with resultant ascites; often a late presentation of disease. It is more often seen as a presenting symptom of peritoneal mesothelioma.
63
Ix for mesothelioma
CXR - unilateral pleural effusion, irregular pleural thickening, reduced lung volumes, and/or parenchymal changes related to asbestos exposure (e.g., lower zone linear interstitial fibrosis)
CT - pleural thickening and/or discrete pleural plaques, pleural and/or pericardial effusions; enlarged hilar and/or mediastinal lymph nodes; chest wall invasion and/or spread along needle tracts can occur
Pleural biopsy - specimen for pathological diagnosis
Possible to do PET scan or MRI or VATS
Or Immunohistochemistry - positive results for certain markers (e.g., calretinin, keratins 5/6, and nuclear WT1) make mesothelioma more likely, while positive results for other markers (e.g., CEA, EPCAM, claudin 4, TTF-1) make mesothelioma less likely
64
Rx of mesothelioma
Operable:
Surgery +/- pre+postop chemo
+/- radiotherapy
Inoperable:
Chemotherapy
+/- radiotherapy
+ palliative procedures and supportive care
Pleurodesis, defined as the artificial obliteration of the pleural space, can be performed to prevent re-accumulation of pleuritic fluid.
65
Prognosis of mesothelioma
Despite advances in treatment, malignant pleural mesothelioma remains a highly lethal malignancy. Overall, the median survival is 10 to 15 months, with only 5% to 10% of patients alive 5 years after diagnosis
In patients with unresectable malignant pleural mesothelioma, median survival with optimal chemotherapy is about 12.3 months, but progression and death is inevitable.
Local disease progression can lead to chest pain, dyspnoea, dysphagia, and, eventually, failure to thrive. Distant metastases are also common, causing site-specific symptoms.
66
Complications of mesothelioma
```
Surgical / radio complications
Radiation pneumonitis
Chemo induced harm toxicity
Post-op mortality
Local invasion of structures
Distant metastasis
```
67
A 72-year-old man presents to his primary care physician with a history of increasing shortness of breath over a period of several months. Before his retirement he was a construction worker. Physical examination reveals decreased breath sounds in the right lung base associated with dullness to percussion.
mesothelioma
Although the most common presentation of malignant pleural mesothelioma is shortness of breath associated with a pleural effusion, patients can also present with a cough, chest pain, and progressive fatigue. Some patients may be asymptomatic with an incidental finding of a pleural effusion noted on physical examination or chest x-ray. Abdominal pain and/or distension, with partial small bowel obstruction, is a common presentation of peritoneal mesothelioma.
68
RFs for aspergillosis
```
STRONG
SCT
Severe neutropenia
CGD
Transplantation (solid organs)
Leukaemia
Aplastic anaemia
Aspergilloma
```
```
WEAK
Advanced chronic lung disease
Primary immunodeficiency
HIV
DM
Malnutrition
Severe burns
MM
Age >55
Smoking
```
69
Rx of aspergillosis
Suspected invasive aspergillosis:
amphotericin B liposomal: 3-5 mg/kg intravenously once daily
OR
amphotericin B lipid complex: 5 mg/kg intravenously once daily
OR
caspofungin: 70 mg intravenously on day 1, followed by 50 mg once daily
+/- surgical resection of the infected focus
70
Prognosis of aspergillosis
Successful outcome depends upon:
Early diagnosis and consequent early initiation of antifungal therapy
Restoration of underlying immunological deficiency.
With the availability of tools for early diagnosis (e.g., high-resolution CT scan, fungal biomarkers), the outlook has considerably improved. In addition, antifungal drugs such as voriconazole are more effective and better tolerated than amphotericin B
After successful therapy, Aspergillus remains quiescent/dormant until immunosuppression is restarted. The estimated risk of relapse is 20% in those with a prior history of aspergillosis receiving myeloablative chemotherapy. In stem cell recipients with a prior history of aspergillosis, the infection may relapse when immunosuppressive therapy is reintroduced or increased. In such cases, secondary prophylaxis with voriconazole may be reasonable.
71
Complications of aspergillosis
```
Life threatening haemoptysis
Disseminated infection
Severe hypoxia
Obstructive sleep apnoea
Pericarditis
```
72
A 65-year-old man underwent induction chemotherapy for recently diagnosed acute myelogenous leukaemia. Antimicrobial prophylaxis included norfloxacin, fluconazole, and aciclovir. During chemotherapy-induced neutropenia, he received empirical antibiotic therapy for the fever without an obvious source of infection. Blood cultures were negative and fever subsided. During the third week of neutropenia, fever recurred with dry cough and left-sided pleuritic pain. Physical examination demonstrated no significant abnormalities. Blood cultures remained negative. CXR was normal. However, a high-resolution CT scan of his chest revealed a 2 cm peripheral nodule with a surrounding 'halo' sign in the left upper lobe.
aspergillosis
Invasive sinus disease may present with headache, congestion, or sinus tenderness. Extension of sinus disease into the eye/brain may lead to proptosis, cranial nerve palsies, altered mental status, and seizures. Concomitant involvement of sinus and lungs may occur. Skin involvement is not uncommon, with single or multiple discrete, erythematous, mildly tender nodules of varying sizes. Direct trauma to the skin may result in local invasion, producing a single lesion.
Aspergilloma is usually asymptomatic. Patients may occasionally present with haemoptysis.
73
A 67-year-old man with COPD presents with recent changes in his CXR. He has shortness of breath that has not changed from his baseline status. On examination, he is afebrile with clinical evidence of chronic lung disease. The CXR reveals a right upper lobe cavitary lesion with an intracavitary mass and adjacent pleural thickening.
aspergillosis
Invasive sinus disease may present with headache, congestion, or sinus tenderness. Extension of sinus disease into the eye/brain may lead to proptosis, cranial nerve palsies, altered mental status, and seizures. Concomitant involvement of sinus and lungs may occur. Skin involvement is not uncommon, with single or multiple discrete, erythematous, mildly tender nodules of varying sizes. Direct trauma to the skin may result in local invasion, producing a single lesion.
Aspergilloma is usually asymptomatic. Patients may occasionally present with haemoptysis.
74
Define aspergillosis
Invasive aspergillosis (IA) is caused by filamentous fungi of the Aspergillus species, which are found ubiquitously in soil. Inhalation of the aerosolised conidia (spores) causes the infection.
Mostly affects immunocompromised patients (e.g., stem cell transplant recipients, prolonged severe neutropenia, immunosuppressive therapy). It is rare in immunocompetent hosts.
Clinical findings are non-specific and include fever, cough, and pleuritic pain. High index of suspicion is required for early diagnosis. Lungs, sinuses, brain, and skin are sites of involvement.
High-resolution CT scan and serum Aspergillus galactomannan antigen test are useful tests for early diagnosis.
Voriconazole is the antifungal agent of choice. Lipid-based formulations of amphotericin B are an alternative.
Early diagnosis and therapy significantly improve prognosis of patients with IA.
Aspergilloma forms in pre-formed lung cavities. It is usually asymptomatic. Diagnosis is generally made by CXR or CT scan. Antifungal drugs have been shown not to be beneficial. Surgery may be required in patients with severe haemoptysis.
75
Define hypersensitivity pneumonitis
An inflammation of the alveoli and distal bronchioles caused by an immune response to inhaled allergens.
Occupational exposure to organic dust is the key epidemiological factor - most commonly including Actinomycetesbacteria, animal proteins, or reactive chemicals.
Diagnosis requires a high index of suspicion when evaluating individuals with interstitial lung disease or recurrent flu-like illness.
Immunological reaction to inhaled antigen is corroborative.
No pathognomonic tests.
Treatment involves avoidance of causative agent and use of corticosteroids.
Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is the result of non-IgE mediated immunological inflammation. HP is caused by repeated inhalation of non-human protein, which can be of natural plant or animal origin or can be the result of a chemical conjugated to a human airway protein, such as albumin. The inflammation of HP manifests itself in the alveoli and distal bronchioles. The clinical manifestations of HP depend on the concentration and frequency of exposure. The clinical syndromes - acute, sub-acute, and chronic HP - present differently.
76
Epidemiology of hypersensitivity pneumonitis
The prevalence of HP is not precisely known. It most probably varies with the antigen, the exposure concentration, and as yet unidentified host factors. In the past, the prevalence among Wisconsin dairy farmers was reported as being 2% to 8%. However, with remedying of the damp conditions leading to farmer's lung, that prevalence has dropped. It has been estimated that HP occurs in 6% to 21% of pigeon breeders. One Danish study reported that the hazard ratio (HR) for pigeon breeders developing HP is 14.36 (95% CI: 8.10-25.44).
77
Aetiology of hypersensitivity pneumonitis
The two most commonly reported agents are bacteria (e.g., thermophilic Actinomycetes, responsible for a variety of syndromes including farmer's lung, bagassosis, and mushroom picker's lung) and animal proteins (e.g., avian proteins responsible for diseases including pigeon breeder's lung, bird fancier's lung, and budgerigar fancier's disease), with exposure to large farm animals also implicated.
Since the beginning of the 21st century in the UK, exposure to metal-working fluid has become the most common cause of occupational HP, accounting for about half of all cases.
Ingested drugs such as nitrofurantoin, methotrexate, roxithromycin, and rituximab can cause drug-induced hypersensitivity pneumonitis syndrome.
78
RFs for hypersensitivity pneumonitis
```
WEAK
Smoking
Viral infections
Exposure to:
Avian protein allergen
Mould antigen
Bacterial antigen
Diisocyanate (epoxy resin_
Paint refinisher
Metla working fluid
Nitrofurantoin, methotrexate, rituximab, roxithromycin
Ayurvedic
```
79
Sx of hypersensitivity pneumonitis
```
COMMON
Dyspnoea - Almost always present; with the acute forms it is typically episodic, associated with fevers, cough, and malaise.
Non-productive OR productive cough
Fever/chills
Malaise
WL/anorexia
Bibasilar rales
Diffuse rales
Clubbing
```
80
Rx of hypersensitivity pneumonitis
1. Avoidance of antigen
+/- corticosteroid taper - prednisolone: 0.5 to 1 mg/kg/day orally, taper dose by 5-10 mg/day every other day for 6 weeks
2. Chronic symptoms = long term low dose corticosteroids
prednisolone: 10 mg orally once daily on alternate days
81
Prognosis of hypersensitivity pneumonitis
There are limited studies. In patients with acute HP, avoidance will result in a good prognosis. In patients with sub-acute or chronic HP, the prognosis depends not only on the ability to avoid the causative antigen but also on the lung function at diagnosis, and the amount of fibrosis that has already occurred. If there is significant fibrosis, it is unlikely that pulmonary function tests will normalise. In the absence of antigen avoidance, deaths have been reported in individuals diagnosed with farmer's lung and pigeon breeder's disease.
82
Complications of hypersensitivity pneumonitis
Deterioration in lung function
Hypoxaemia
Death
83
A 38-year-old man presents with fever of 38.5°C (101.2°F), chills, myalgias, non-productive cough, and dyspnoea. Other than tachypnoea, tachycardia, and bibasilar rales, the rest of the physical examination is normal. He reports that this happens almost every month the day after he cleans out the bird cages in which he keeps the pigeons that he breeds and races.
hypersensitivity pneumonitis
Less common presentations are the sub-acute and chronic forms. The sub-acute form can occur when there is an intermittent, moderate level of exposure: for example, in a home with a leaky roof that harbours thermophilic Actinomycetes. An individual with sub-acute HP will probably present after weeks or months of exposure with symptoms of dyspnoea, productive cough, and malaise with no temporal relationship to exposure. In the chronic form, the exposure is low and occurs over months to years. An example is a person living in an apartment above, and sharing a ventilation system with, a pet store that specialises in birds. After years of living in the apartment, the individual with HP may present with vague, insidious symptoms such as dyspnoea, weight loss, malaise, and cough. Clubbing occurs in approximately half of such HP patients.[7][8]
84
Define IPF
Idiopathic pulmonary fibrosis (IPF) is a rare, chronic, life-threatening disease that manifests over several years and is characterised by the formation of scar tissue within the lungs and progressive dyspnoea. It is the most common interstitial lung disease among the idiopathic interstitial pneumonias, which share clinical features of shortness of breath, diffuse pulmonary infiltrates on imaging, and varying degrees of inflammation, fibrosis, or both on lung biopsy.
Idiopathic pulmonary fibrosis (IPF) is a rare form of fibrotic lung disease with no known aetiology that progresses over the course of several years. It is characterised by scar tissue formation within the lungs, dyspnoea, and a significantly shortened lifespan after diagnosis.
Although the aetiology is unknown, cigarette smoking and certain environmental exposures have been implicated in the development of IPF.
In the absence of findings that suggest an alternative disease process, IPF can be diagnosed on clinical grounds when an appropriate history of progressive symptoms (typically dyspnoea and cough) is accompanied by characteristic x-ray findings and restrictive physiology on pulmonary function testing.
Initial therapy is with an antifibrotic agent. Important supportive measures include smoking cessation, pulmonary rehabilitation, and supplemental oxygen when appropriate. Some patients may be eligible for lung transplantation.
85
Epidemiology of IPF
14.0 and 42.7 cases per 100,000 people
Approximately two-thirds of patients with IPF are over 60 years of age at the time of presentation, with a mean age at diagnosis of between 60 and 70 years.
IPF is more common among men than among women
No ethnic, regional, or racial predilection for the development of IPF has been identified
86
Aetiology of IPF
The cause of IPF is not known. A possible theory is that an unidentified insult causes damage to the alveolar epithelium, endothelium, and basement membrane. Cigarette smoke, organic or metal dust, gastro-oesophageal reflux disease (GORD), diabetes, and infection have each been associated with IPF; however, the exact inciting exposure or exposures remain unknown
There is evidence that a history of gastro-oesophageal reflux may predispose to the development of IPF, presumably through injury induced by acid aspiration. A small case-control study using oesophageal pH monitoring found that 16 out of 17 patients with IPF had an abnormal oesophageal exposure to gastric acid, compared with only 50% of control patients.
87
RFs for IPF
```
STRONG
Increased age
Male
FHx
Cig smoking
```
```
WEAK
Organic and inorganic dust exposure
GORD
Infection
DM
```
88
Sx of IPF
Dyspnoea - Dyspnoea on exertion is usually the most prominent and disabling symptom
Cough (non-productive)
Crackles - End-expiratory, basilar crackles are almost universally present on lung examination
NB- Asymptomatic patients may be found on routine clinical lung examination to have bi-basilar inspiratory crackles without signs or symptoms of congestive heart failure. These patients may be evaluated first by a cardiologist, based on a presumed diagnosis of congestive heart failure.
WL, fatigue and malaise
Clubbing (50%)
89
Ix for IPF
CXR - basilar, peripheral, bilateral, asymmetrical, reticular opacities
HRCT - basilar- and subpleural-predominant areas of increased reticulation, honeycombing, and possible traction bronchiectasis or bronchiolectasis
ANA - normal or mildly elevated (Titres of >1:160 suggest the possibility that a collagen vascular disease might be responsible for the interstitial lung disease.)
RF - Mildly elevated titres may occur in 10% to 20% of patients with IPF.
anti-CCP - The presence of circulating anti-cyclic citrullinated peptide antibodies suggests that a collagen vascular disease might be responsible for the interstitial lung disease.
Myositis panel - normal (The presence of myositis-specific antibodies suggests that a collagen vascular disease might be responsible for the interstitial lung disease.)
90
Rx of IPF
ACUTE EXACERBATION
High-dose corticosteroid
ONGOING
Smoking cessation + pulmonary rehab + O2
Anti-fibrotic:
pirfenidone: 267 mg orally three times daily initially on days 1-7, followed by 534 mg three times daily on days 8-14, then 801 mg three times daily thereafter
OR
nintedanib: 150 mg orally twice daily
PPI
lansoprazole: 15 mg orally once or twice daily
OR
omeprazole: 20 mg orally once or twice daily
OR
pantoprazole: 20 mg orally once or twice daily
2. LUNG TRANSPLANTATION
91
Prognosis of IPF
Patients with IPF experience progressive dyspnoea and functional decline over time. The median survival time has been estimated to be 2-5 years from the time of diagnosis, and most patients will die from their disease.
The annual incidence of acute exacerbations among IPF patients is not well described, but estimates have ranged from 5% to 19%. These patients have a high mortality rate of 49% to 78%
92
Complications of IPF
```
PHTN
Lung cancer
GORD
Pneumonia
Pneumothorax
PE
DVT
Acute coronary syndrome
```
93
A 65-year-old man presents with gradually progressive dyspnoea on exertion and a non-productive cough. He has no history of underlying lung disease and no features that would suggest an alternative aetiology for his cough and dyspnoea. He has no history of joint inflammation, skin rashes, or other features of a systemic inflammatory disease such as lupus or rheumatoid arthritis. He takes no medications and has no environmental exposures to organic allergens such as mould. On examination, he has fine crackles audible over his lung bases bilaterally; however, he has no lower-extremity oedema, elevations in jugular venous pressure, or any other findings to suggest volume overload. He has clubbing of his fingers.
IPF
Patients may also present with mild or even absent symptoms but have a chest x-ray or a computed tomography scan of the chest obtained for other reasons showing bilateral, basilar-predominant interstitial opacities. Similarly, asymptomatic patients may be found on routine clinical lung examination to have bi-basilar inspiratory crackles without signs or symptoms of congestive heart failure. These patients may be evaluated first by a cardiologist based on a presumed diagnosis of congestive heart failure.
94
A 72-year-old man with a history of cigarette smoking presents with mild shortness of breath. He is treated initially with inhaled bronchodilators for a presumed diagnosis of chronic obstructive lung disease but has no symptomatic improvement. Pulmonary function tests are performed and show restriction rather than obstruction, along with impaired diffusing capacity for carbon monoxide. A follow-up chest radiograph shows prominent bi-basilar interstitial markings.
IPF
Patients may also present with mild or even absent symptoms but have a chest x-ray or a computed tomography scan of the chest obtained for other reasons showing bilateral, basilar-predominant interstitial opacities. Similarly, asymptomatic patients may be found on routine clinical lung examination to have bi-basilar inspiratory crackles without signs or symptoms of congestive heart failure. These patients may be evaluated first by a cardiologist based on a presumed diagnosis of congestive heart failure.
95
Define obstructive sleep apnoea
Obstructive sleep apnoea (OSA) is characterised by episodes of complete or partial upper airway obstruction during sleep. Episodic airway obstruction is usually associated with oxyhaemoglobin desaturations and arousals from sleep. The symptoms of sleep apnoea include chronic snoring, insomnia, gasping and breath holding, unrefreshing sleep, and daytime sleepiness. ≥15 episodes/hour
Symptoms include loud snoring, gasping during sleep, apnoeas, unrefreshing sleep, and excessive daytime sleepiness.
Obesity, retro- or micrognathia, oropharyngeal narrowing, and macroglossia are common physical features.
Diagnosis is established using clinical evaluation plus polysomnography or portable sleep tests.
Positive airway pressure or oral appliances are non-invasive treatment options.
In patients unable to adhere to medical therapy or with discrete anatomical sites of obstruction, soft tissue and/or skeletal surgery may be selected for treatment of obstructive sleep apnoea.
Complications of untreated obstructive sleep apnoea include increased risk of premature death, MI, dysrhythmias, stroke, HTN, motor vehicle accidents, metabolic syndrome, and neurocognitive dysfunction.
Complications of continuous positive airway pressure (CPAP) treatment include sleep disturbance, rhinitis, dermatitis, conjunctivitis, aerophagia, and dyspnoea. Complications of oral appliance therapy include occlusal changes and facial pain. Complications of surgery include bleeding, haematoma, velopharyngeal insufficiency, pharyngeal stenosis, dysphagia, airway obstruction, and, very rarely, death.
96
Epidemiology of obstructive sleep apnoea
4% of men and 2% of women
OSA is more common with increasing age, and, per 10-year increment, a greater increase in the odds of OSA is seen in women.
97
Aetiology of obstructive sleep apnoea
Airway narrowing may be triggered by neuromuscular mechanisms within an anatomically small upper airway. Anatomical narrowing of the pharynx may be mediated by maxillomandibular anomalies or adenotonsillar hypertrophy
98
RFs for obstructive sleep apnoea
```
STRONG
Obesity Male
PM women
Large neck circumference
Maxillomandibular abnormalities
Increased volume of soft tissues
Fix OSA
Chronic snoring
PCOS
Hypothyroidism
Downs
Increasing age
Black, hispanic or asian
Tobacco
```
WEAK
Nasal obstruction
Levels of sex hormones
Alcohol use
99
Sx of obstructive sleep apnoea
```
Obesity
Male sex
Excessive daytime sleepiness
Episodic apnoea + gasping
Restless sleep
Insomnia
Macroglossia
Chronic snoring
CV disease
Weight gain
Large neck circumference
Endocrine disorders
Hx difficult intubation
Mood disorders
ED
Dyspepsia
Dry mouth
Nocturnal sweating
```
100
Ix for obstructive sleep apnoea
Polysomnography
Oral + nasal endoscopy - Routinely performed to exclude presence of lesions, such as nasal polyps or tumours (pharyngeal, parapharyngeal, or laryngeal tumours), and to assess structures and sites mediating obstruction, especially in a CPAP-intolerant patient. Endoscopy may also be used for oral appliance therapy assessment
101
Rx of obstructive sleep apnoea
WEIGHTLOSS
1. CPAP + improvement of adherence
2. Oral appliance therapy
ie Mandibular repositioning appliances (MRAs) or tongue retainers
3. SURGERY - widening of airways
4. Bariatric surgery
+/- modafinil if hypersomnolent
Possible to use implantable hypoglossal stimulation
102
Prognosis of obstructive sleep apnoea
Patients efficiently treated may report improvements in alertness and some improvement in quality of life, mood, and cognitive function. Mortality and morbidity from cardiovascular disease is also reduced. Risk of motor vehicle accidents seems to be lower in treated versus untreated patients.
103
Complications of obstructive sleep apnoea
```
Impaired glucose metabolism
CV disease
Depression
Motor vehicle accidents
Cognitive dysfunction
Increased mortality
```
104
A 41-year-old obese man presents with loud chronic snoring and gasping episodes during sleep. His wife has witnessed episodic apnoea. He reports unrefreshing sleep, multiple awakenings from sleep, and morning headaches. He has excessive daytime sleepiness, which is interfering with his daily activities, and he narrowly avoided being involved in a motor vehicle accident. His memory is also affected. He has been treated for hypertension, gastro-oesophageal reflux, and type 2 diabetes.
obstructive sleep apnoea
105
Aetiology of pneumoconiosis
Silica
Coal
Beryllium
106
Rx of pneumoconiosis
Acute silicosis - lung lavage
Acute berylliosis - corticosteroids
ONGOING FOR ALL
Smoking cessation and removal of occupational exposure
Pulmonary rehabilitation
Patients should be advised of their legal rights regarding compensation.
Chronic berylliosis - prednisolone: 40-70 mg orally once daily initially, taper gradually according to response
Hypoxia = O2 therapy
ESresp failure = referral for lung transplantation
107
Prognosis of pneumoconiosis
Prognosis is related to extent of fibrosis noted at diagnosis and past cumulative exposure. Many patients with pneumoconiosis will not progress and will go on to die from other conditions.
Beryllium sensitisation
Over 5 years, one third of patients with evidence of sensitisation, a positive beryllium lymphocyte proliferation test, will go on to develop granulomas in their lung tissue. However, these people may still never develop symptoms or changes on pulmonary function testing
108
Complications of pneumoconiosis
```
COPD
Chronic renal failure
Lung cancer
Cor pulmonale
Acute bronchitis / pneumonia
Rheumatoid Arthritis
Scleroderma
Wegeners
Tuberculosis
```
109
A 76-year-old retired steelworker has shortness of breath with activity that has been gradually getting worse, and a chronic cough. He denies chest pain. He has a 45-pack/year smoking history, but stopped aged 50. There is no family history of lung disease. He does not take any respiratory medication on a regular basis. He has noticed that he wheezes when he has an upper respiratory infection (URI), and his doctor once prescribed him an inhaler. He is also bothered by joint swelling and stiffness. Lung auscultation is normal. (This case is a common clinical presentation of silicosis or coal workers' pneumoconiosis.)
pneumoconiosis
A rare presentation is with a relatively acute onset of marked shortness of breath. This is typical of acute silicosis with alveolar proteinosis, as well as acute berylliosis, which presents as an acute pneumonitis. Alternatively, patients may develop pulmonary tuberculosis (TB), a complication of silica exposure, and present with haemoptysis, night sweats, and fever. Presentation may also be with predominantly non-respiratory symptoms, such as symptoms of scleroderma or rheumatoid arthritis, which are less-common complications of silica or coal exposure.
110
A 35-year-old man who works machining beryllium-copper alloy for the electronics industry is concerned about the possibility of adverse health effects from beryllium, which is a component of the metal he is machining. He has heard about a blood test that can be used for diagnosing beryllium disease. He is not sure if he has had some increased shortness of breath with exercise. He has never smoked cigarettes. He has no personal or family history of allergies or asthma. Lung auscultation is normal. (This case is a common clinical presentation of chronic beryllium disease.)
pneumoconiosis
A rare presentation is with a relatively acute onset of marked shortness of breath. This is typical of acute silicosis with alveolar proteinosis, as well as acute berylliosis, which presents as an acute pneumonitis. Alternatively, patients may develop pulmonary tuberculosis (TB), a complication of silica exposure, and present with haemoptysis, night sweats, and fever. Presentation may also be with predominantly non-respiratory symptoms, such as symptoms of scleroderma or rheumatoid arthritis, which are less-common complications of silica or coal exposure.
111
Define sarcoidosis
Sarcoidosis is a chronic granulomatous disorder of unknown aetiology, commonly affecting the lungs, skin, and eyes. It is characterised by accumulation of lymphocytes and macrophages and the formation of non-caseating granulomas in the lungs and other organs. Although lungs and lymph nodes are involved in more than 90% of patients, virtually any organ can be involved. It has a bimodal age distribution with 2 peaks in the third and fifth decades. The clinical course is often heterogeneous and unpredictable.
Sarcoidosis is a diagnosis of exclusion of granulomatous lung diseases, including tuberculosis and histoplasmosis.
Typical history and biopsy from affected organs are essential for the diagnosis.
Treated with topical corticosteroids for mild local cutaneous disease. Systemic corticosteroids are the mainstay of treatment for severe disease.
Carries a mortality of 1% to 6%.
Poorer prognosis if black ancestry, chronic pulmonary involvement, lupus pernio, or chronic hypercalcaemia.
Spontaneous remissions occur in 55% to 90% of patients with stage I, 40% to 70% of patients with stage II, and about 20% of patients with stage III disease, but no remissions are expected in stage IV.
112
Epidemiology of sarcoidosis
6 per 100k
B>W
Scandinavian people
Women are more likely to have eye and neurological involvement and have erythema nodosum, whereas men are more likely to be hypercalcaemic. Black people are more likely to have skin manifestations (other than erythema nodosum) and have eye, liver, bone marrow, and extrathoracic lymph node involvement.
113
Aetiology of sarcoidosis
Aetiology is unknown. However, several aetiological factors have been suggested, including genetic, immunological, and infectious causes (e.g., viruses, Borrelia burgdorferi, Propionibacterium acnes, Mycobacterium tuberculosis, and Mycoplasma).
The characteristic finding is the presence of non-caseating granulomas with multinucleated giant cells in the centre.
114
RFs for sarcoidosis
STRONG
20-40
FHx
Scandinavian
```
WEAK
Female
Non-smokers
Black ancestry - uveitis
Puterorico - lupus pernio
European - erythema nodosum
```
115
Sx of sarcoidosis
```
COMMON
Cough (Non-productive)
Dyspnoea
Chronic fatigue
Arthralgia - No synovial thickening on examination
Wheezing
Rhonchi
Lymphadenopthy
Photophobia
Red painful eye
Blurred vision
```
```
UNCOMMON
Erythema nodosum
Lupus pernio
Conjunctival nodules
Facial palsy
Chest wall pain
Haemoptysis
WL
Low-grade fever
HB + arrythmias
Headache
Hepatomegaly
Seizures
Symptoms and Sx of pituitary lesion
```
116
Ix for sarcoidosis
CXR - hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates; pleural effusions (rare) and egg shell calcifications (very rare) may be seen
Calcium - hypercalcaemia
ACE - elevated (50%)
PFTs - monitor disease
ECG - conduction defects, exclude cardiac involvement
FBC - anaemia in 4%-20%; leukopenia in 40%
Urea + creatinine - elevated
Liver enzymes - Asymptomatic aminotransferase (AST and ALT) elevation possible.
117
Rx of sarcoidosis
ACUTE
IV corticosteroids - methylprednisolone sodium succinate: 40 mg intravenously every 6 hours until oral intake possible
+ ventilation + O2
ONGOING
STAGE 1 = observe
Or oral or inhaled corticosterois
2. Other immunosuppressants
methotrexate: 7.5 mg orally once weekly on the same day of each week initially, increase by 2.5 mg/week increments every 2 weeks, maximum 15 mg/week
OR
azathioprine: 50 mg orally once daily for 2 weeks , increase by 25 mg/day increments every 2-3 weeks, maximum 200 mg/day
Secondary options
hydroxychloroquine: 200-400 mg orally once daily
+/- O2
3. Transplantation
118
Complications of sarcoidosis
```
Haemoptysis
Corticosteroid related hyperglycaemia
PAH
Glaucoma
Osteoporosis (ster)
Hepatic toxicity from methotrexate + azath
CHF
Meningeal disease
Sinal canal disease
Neuropathy
Myopathy
Cataract
Vascular retinitis
Optic atrophy
Vision loss
Pituitary lesion
Heart block
Infection
Ventricular arrythmias
Cranial neuropathies
```
119
A 29-year-old woman presents with shortness of breath, cough, and painful red skin lesions on the anterior surface of the lower part of both legs. CXR reveals bilateral hilar lymphadenopathy with pulmonary infiltrates.
sarcoidosis
Multisystem involvement is characteristic, but pulmonary involvement usually dominates. Skin, eyes, and peripheral lymph nodes are involved in 15% to 30% of patients. Clinically significant involvement of spleen, liver, heart, CNS, bone, or kidney occurs in a few patients. Incidental diagnosis on routine CXR also occurs.
120
A 35-year-old woman presents with skin lesions around her nose, which are indurated plaques with discoloration. She also reports a red, moderately painful right eye with blurred vision and photophobia.
sarcoidosis
Multisystem involvement is characteristic, but pulmonary involvement usually dominates. Skin, eyes, and peripheral lymph nodes are involved in 15% to 30% of patients. Clinically significant involvement of spleen, liver, heart, CNS, bone, or kidney occurs in a few patients. Incidental diagnosis on routine CXR also occurs.
121
A 35-year-old woman presents with skin lesions around her nose, which are indurated plaques with discoloration. She also reports a red, moderately painful right eye with blurred vision and photophobia.
sarcoidosis
Multisystem involvement is characteristic, but pulmonary involvement usually dominates. Skin, eyes, and peripheral lymph nodes are involved in 15% to 30% of patients. Clinically significant involvement of spleen, liver, heart, CNS, bone, or kidney occurs in a few patients. Incidental diagnosis on routine CXR also occurs.
122
Define pulmonary tuberculosis
Pulmonary tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. In many cases, M tuberculosis becomes dormant before it progresses to active TB. It most commonly involves the lungs and is communicable in this form, but may affect almost any organ system including the lymph nodes, CNS, liver, bones, genitourinary tract, and gastrointestinal tract.
A notifiable disease.
Specific risk factors include having lived in Asia, Latin America, Eastern Europe, or Africa for years; exposure to an infectious TB case; residence in an institutional setting and homelessness.
Symptoms may include cough, fever, and weight loss.
If clinical suspicion of pulmonary TB, a patient should be isolated, a CXR should be obtained, 3 sputum samples should be collected for acid-fast bacilli smear and culture, and nucleic acid amplification test (NAAT) should be performed on at least one respiratory specimen.
Directly observed therapy is highly recommended and is particularly indicated in groups where adherence can not be assumed.
Early recognition and implementation of effective treatment for infectious TB is crucial in interrupting TB transmission.
123
Epidemiology of pulmonary tuberculosis
According to WHO data, TB is the ninth leading cause of death worldwide, and is the leading cause of death from a single infectious agent.
n 2016, an estimated 10.4 million people developed TB, and there were an estimated 1.3 million TB deaths among HIV-negative people and 374,000 TB-related deaths among HIV-positive people.[1] More than half of all cases (56%) were in five countries: India, Indonesia, China, the Philippines, and Pakistan, and the majority of deaths (85% of HIV-negative and HIV-positive TB deaths) were in the WHO African Region and South-East Asia Region
124
Aetiology of pulmonary tuberculosis
The development of TB requires infection by M tuberculosis and inadequate containment by the immune system. Patients infected with M tuberculosis who have no clinical, bacteriological, or radiographic evidence of active TB are said to have latent TB infection. Active TB may occur from re-activation of previously latent infection or from progression of primary infection.
Transmission of TB occurs from individuals infected with pulmonary (and rarely laryngeal) disease. Infection results from the inhalation of aerosolised droplets containing the bacterium. The likelihood of transmission depends on the infectivity of the source case (e.g., smear status and extent of cavitation on CXR), the degree of exposure to the case (e.g., proximity, ventilation, and the length of exposure), and susceptibility of the person in contact with an infected case.
125
RFs for pulmonary tuberculosis
```
STRONG
Exposure to infection
Birth in an endemic country
HIV infection
Immunosuppressives
Silicosis
Apical fibrosis
```
```
WEAK
Malignancy
ESRD
IVDU
Malnutrition
Alcoholism
DM
High-risk conjugate settings
Low socio-economic
Age
Tobacco
```
126
Sx of pulmonary tuberculosis
```
COMMON
Cough - Duration over 2 to 3 weeks; initially dry later productive.
Fever
Anorexia
WL
Malaise
Haemoptysis
Night sweats
```
```
UNCOMMON
Chest examination may be normal in mild/moderate disease. Possible findings include crackles, bronchial breath sounds, or amphoric breath sounds (distant hollow breath sounds heard over cavities).
Asymptomatic
Dyspnoea
Clubbing
Erythema nodosum
```
127
Ix for pulmonary tuberculosis
CXR - Typically presents as fibronodular opacities in upper lobes with or without cavitation. Atypical pattern includes opacities in middle or lower lobes, hilar or paratracheal lymphadenopathy, and/or pleural effusion.
AFB sputum smear - positive for acid-fast bacilli (AFB)
Sputum culture - positive; no growth; or other mycobacteria
FBC - raised WBC; low Hb
NAAT - positive forM tuberculosis
128
Rx of pulmonary tuberculosis
LATENT
isoniazid: 5 mg/kg orally once daily for 6-9 months, maximum 300 mg/dose; or 15 mg/kg orally twice weekly for 6-9 months, maximum 900 mg/dose
and
pyridoxine: consider 25 mg orally once daily
ESTABLISHED
isoniazid: 5 mg/kg orally once daily, maximum 300 mg/dose; or 15 mg/kg orally twice weekly, maximum 900 mg/dose; or 15 mg/kg orally three times weekly, maximum 900 mg/dose
and
pyridoxine: 25 mg orally once daily
and
rifampicin: 10 mg/kg orally once daily, maximum 600 mg/dose; or 10 mg/kg orally twice weekly, maximum 600 mg/dose; or 10 mg/kg orally three times weekly, maximum 600 mg/dose
and
pyrazinamide: dose is based on lean body weight and tablet formulation available; consult specialist, guidelines, or local protocols for guidance on dose
and
ethambutol: dose is based on lean body weight and tablet formulation available; consult specialist, guidelines, or local protocols for guidance on dose
FOR 6 months
THEN:
isoniazid: 5 mg/kg orally once daily, maximum 300 mg/dose; or 15 mg/kg orally three times weekly, maximum 900 mg/dose
and
pyridoxine: 25 mg orally once daily
and
rifampicin: 10 mg/kg orally once daily, maximum 600 mg/dose; or 10 mg/kg orally three times weekly, maximum 600 mg/dose
FOR 18 weeks
IF multi-drug resistant - contact micro + specialist
The conservative approach dictates that patients are considered infectious until 3 consecutive sputum acid-fast bacilli smears are negative, they have been on standard therapy for at least 2 weeks, and they show clinical improvement on TB therapy.
129
Prognosis of pulmonary tuberculosis
Without treatment the mortality rate of TB exceeds 50%; however, TB is a treatable disease. In the US in 2009 there were 529 deaths because of TB out of 11,528 reported cases, a case fatality rate of 4.6%. Risk factors for death include increased age, delay in diagnosis of TB, extent of radiographic involvement, the need for mechanical ventilation, ESRD, diabetes, and immunosuppression.
In general, patients with treated TB can expect to do well with minimal or no sequelae.
130
Complications of pulmonary tuberculosis
```
Transmission of TB
IRIS
ARDS
Pneumothorax
Empyema
Bronchiectasis
Extensive lung destruction
RML syndrome
Haemoptysis
```
131
A 34-year-old man presents to his primary care physician with a 7-week history of cough that he describes as non-productive. He has had a poor appetite during this time and notes that his clothes are loose on him. He has felt febrile at times, but has not measured his temperature. He denies dyspnoea or haemoptysis. He is originally from the Philippines. He denies any history of TB or TB exposure. Physical examination reveals a thin, tired-appearing man but is otherwise unremarkable.
pulmonary tuberculosis
The presentation of pulmonary TB is varied, as patients may present early or late in the course of the disease, or have different host factors (e.g., HIV, age) that may impact disease presentation. Classic findings, including haemoptysis, night sweats, and weight loss, make the diagnosis obvious, but may be absent. A number of features associated with the misdiagnosis of TB include lack of pulmonary symptoms, a sputum smear that is acid-fast bacilli-negative, negative tuberculin skin test, atypical CXR findings, and the presence of other diseases that may alter immune status. Careful attention to epidemiological risk factors (e.g., residence or work in a congregate setting, birth or long-term living in TB-prevalent counties, history of latent TB infection, or recent exposure to an infectious case) will often lower the threshold to consider TB as part of the differential diagnosis.
132
Define small-cell lung cancer
Small cell lung cancer (SCLC), previously referred to as oat cell carcinoma, is a malignant epithelial tumour arising from cells lining the lower respiratory tract. The tumour cells are small and densely packed, with scant cytoplasm, finely granular nuclear chromatin, and absence of nucleoli.
Small cell lung cancer (SCLC) is an aggressive malignancy. Approximately two-thirds of patients have evidence of distant metastasis at presentation. It primarily develops in older adult smokers.
Most common presenting symptoms are cough, chest pain, haemoptysis, dyspnoea, and weight loss.
A suspicious lung mass should be biopsied during bronchoscopy or CT-guided transthoracic needle aspiration.
Staging studies should include chest/abdomen CT and brain MRI (preferred) or head CT, with mediastinoscopy and/or bone marrow aspirate and biopsy in selected cases. If disease appears to be confined to the chest, positron emission tomography (PET)-CT can be done to assess for distant metastases. Bone scan can be done if PET-CT is not available. Accurate staging is very important for treatment selection.
Localised disease (defined as disease that can be contained within a radiation portal) should be treated with concurrent chemotherapy and radiotherapy. Radiotherapy should be started as early as possible. Surgery should be offered to patients with clinical T1N0 or T2N0 disease after mediastinoscopy. Extensive-stage disease should be treated with chemotherapy. Palliative radiotherapy may be utilized if necessary. Prophylactic cranial irradiation should be considered for all patients who demonstrate a response to initial therapy and are stable at completion of therapy.
133
Epidemiology of small-cell lung cancer
More than 39,000 deaths are attributed to lung cancer in England and Wales each year.
After adjusting for age, the incidence of lung cancer is about 60% higher in men.
Worldwide, lung cancer is the most common non-cutaneous cancer and is increasing at a rate of 0.5% per year. Lung cancer accounts for over a million deaths annually.
134
Aetiology of small-cell lung cancer
Tobacco exposure continues to be the most important cause of lung cancer and approximately 90% of lung cancer is directly attributable to smoking.
Tobacco smoke contains multiple carcinogens, including polynuclear aromatic hydrocarbons, aromatic amines, N-nitrosamines, and other organic and inorganic compounds.
SCLC comprises approximately 15% of lung cancers and is highly associated with smoking relative to other subtypes of lung cancer.
135
RFs for small-cell lung cancer
STRONG
Tobacco
Environmental tobacco
Radon gas exposure
WEAK
Asbestos exposure
136
Sx of small-cell lung cancer
```
COMMON
Cough
Dyspnoea
Haemoptysis
Chest pain
WL
Fatigue
Pulmonary examination abnormalities - Auscultation of the lungs may demonstrate wheeze, rales, decreased breath sounds, and dullness to percussion.
```
```
UNCOMMON (relating to mets)
Hoarseness
Confusion
Personality changes
Headache
Dysphagia
Bone pain/fractures
Seizures
Cervical or supraclavicular adenopathy
Dilated neck veins
Finger clubbing
Hypertrophic osteoarthropathy
```
137
Ix for small-cell lung cancer
CXR - central mass, hilar lymphadenopathy, pleural effusion
CT CAP - massive lymphadenopathy and direct mediastinal invasion are common features of SCLC; determines extent of disease
Sputum cytology - malignant cells in sputum
Bronchoscopy + biopsy - endobronchial lesions
138
Rx of small-cell lung cancer
Chemotherapy:
cisplatin
and
etoposide
+ Radiotherapy
+ Prophylactic cranial irradiation
+/- surgery - surgical intervention has limited use in SCLC because most patients present with advanced disease.
Relapse = chemoradio
139
Prognosis of small-cell lung cancer
Survival after definitive treatment of SCLC is dependent on stage. The 5-year survival rates are approximately 12% to 24% for limited stage and 1% to 5% for extensive stage.
140
Complications of small-cell lung cancer
```
Post-obstructive pneumonia / hypoxia
Chemo induced haem tox
Superior vena cava syndrome
Paraneoplastic syndromes
Radiation-induced oesophageal injury
Radiation induced injury
Acute/massive haemoptysis
```
141
A 65-year-old man presents with a 2-month history of a dry persistent cough and 4.5 kg unintentional weight loss. He denies fevers, dyspnoea, sore throat, rhinorrhoea, chest pain, or haemoptysis. Past medical history is significant for chronic obstructive pulmonary disease and hypertension. Family history is non-contributory. He smoked 1 pack of cigarettes daily for 40 years but quit 5 years ago. No adenopathy was palpable on examination and breath sounds were diminished globally without focal wheezes or rales.
small-cell lung cancer
Lung cancer can present without symptoms. This is due to the large functional reserve of the lungs and lack of pain fibres within the lung parenchyma. Consequently, lung cancer can present as an incidental mass on chest x-ray or CT. Eventually, patients develop symptoms from local tumour growth within the lung, including cough, dyspnoea, chest pain, and/or haemoptysis.[2][3] Haemoptysis typically consists of blood-tinged sputum. Massive haemoptysis is rare. Invasion of the pleura or chest wall can cause chest pain. Obstruction of major airways can cause dyspnoea, wheezing, or post-obstructive pneumonia. A pneumonia that does not rapidly clear with antibiotics is cause for concern for lung cancer, especially in patients with a tobacco history.
Lung cancer often spreads to mediastinal lymph nodes. Symptoms from mediastinal adenopathy are relatively rare. However, bulky adenopathy can cause hoarseness (impingement of the recurrent laryngeal nerve), paralysis of the diaphragm (impingement of the phrenic nerve), difficulty swallowing (extrinsic compression of the oesophagus), or superior vena cava syndrome, typically characterised by upper extremity and facial oedema, orthopnoea, cough, and venous distension of the neck and chest wall.[4]
SCLC is associated with paraneoplastic syndromes such as Lambert-Eaton myasthenic syndrome, peripheral neuropathy, syndrome of inappropriate ADH secretion, and Cushing's syndrome.[1]
Finger clubbing and hypertrophic osteoarthropathy is less common in SCLC compared with non-small cell lung cancer.[3]
142
Define non-small cell lung cancer
Lung cancer comprises a group of malignant epithelial tumours arising from cells lining the lower respiratory tract. Lung cancer is divided into 2 categories: non-small cell lung cancer (NSCLC) and small cell lung cancer. NSCLC accounts for more than 80% of all lung cancers. There are 3 main types of NSCLC (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma) and these are grouped into further subtypes.
Most common in older adult smokers and ex-smokers. Small tumours in the lung are often asymptomatic, so the majority of patients have either locally advanced or metastatic disease at diagnosis.
Most common presenting symptoms are cough, chest pain, haemoptysis, dyspnoea, and weight loss.
A suspicious lung mass can be biopsied during bronchoscopy or using CT guidance. Staging studies (i.e., CT, PET, mediastinal sampling) are required to determine extent of local or regional disease and to evaluate for metastases.
Treatment depends on stage of disease, histological subtype, molecular genotype, and patient comorbidities. Surgery, radiotherapy, and chemotherapy are the most common modalities, but molecular-targeted therapy is important for specific genotypes and immunotherapy is becoming increasingly important.
143
Epidemiology of non-small cell lung cancer
Worldwide, lung cancer is the most common non-cutaneous cancer and is increasing at a rate of 0.5% per year. Globally, lung cancer accounted for 1.8 million deaths in 2012 and it remains the most common cause of cancer mortality worldwide, with 17.6% of the world total.
Lung cancer is the third most common cancer type in Europe, with NSCLC accounting for 80% of all lung cancer cases.
144
RFs for non-small cell lung cancer
```
STRONG
Tobacco + env
COPD
FHx
Radon
Older age
```
WEAK
Asbestos exposure
145
Sx of non-small cell lung cancer
```
COMMON
Cough
Dyspnoea
Haemoptysis
Chest pain
WL
Fatigue
Pulmonary examination abnormalities - Auscultation of the lungs may demonstrate wheeze, rales, decreased breath sounds, and dullness to percussion.
```
```
UNCOMMON (relating to mets)
Hoarseness
Confusion
Personality changes
Headache
Dysphagia
Bone pain/fractures
Seizures
Cervical or supraclavicular adenopathy
Dilated neck veins
Finger clubbing
Hypertrophic osteoarthropathy
```
146
Ix for non-small cell lung cancer
CXR - variable; may detect single or multiple pulmonary nodule(s), mass, pleural effusion, lung collapse, or mediastinal or hilar fullness
Contrast enhanced CT - shows size, location and extent of primary tumour; evaluates for hilar and/or mediastinal lymphadenopathy and distant metastases
147
Rx of non-small cell lung cancer
```
STAGE 1+2
Surgery
+ Pre-op chemoradio
cisplatin
-- AND --
vinorelbine
or
gemcitabine
or
docetaxel
or
etoposide
```
Post op chemoradio
Stage 3:
Same as above but;
Anti PD-L1 - durvalumab
Or
anti-angiogenic - bevacizumab
148
Prognosis of non-small cell lung cancer
With these caveats, the 5-year survival rates for patients undergoing surgical (pathological) staging are as follows: stage IA: 67%; stage IB: 57%; stage IIA: 55%; stage IIB: 39%; and stage IIIA: 23% to 25%.[181] Survival for clinically staged patients is as follows: stage IA: 61%; stage IB: 38%; stage IIA: 34%; stage IIB: 22% to 24%; stage IIIA: 9% to 13%; stage IIIB: 3% to 7%; and stage IV: 1%.
149
A 65-year-old man presents with a 2-month history of a dry persistent cough and 4.5 kg unintentional weight loss. He denies fevers, dyspnoea, sore throat, rhinorrhoea, chest pain or haemoptysis. Medical history is significant for COPD and hypertension. Family history is non-contributory. He smoked 1 pack of cigarettes daily for 40 years but quit 5 years ago. No adenopathy is palpable on examination and breath sounds are diminished globally without focal wheezes or crackles.
non-small cell lung cancer
Lung cancer can present without symptoms. This is possibly due to the large functional reserve of the lungs and lack of pain fibres within the lung parenchyma. Consequently, lung cancer can present as an incidental mass on chest x-ray or CT. Eventually, patients develop symptoms from local tumour growth within the lung, including cough, dyspnoea, chest pain, and/or haemoptysis. Cough is the most common symptom, followed by dyspnoea. Haemoptysis typically consists of blood-tinged sputum, blood streaks in sputum, or small clots. It is a relatively uncommon symptom (compared with cough and dyspnoea) but more specific for lung cancer. Massive haemoptysis is rare. Invasion of the pleura or chest wall can cause chest pain. Obstruction of major airways can cause dyspnoea, wheezing, or post-obstructive pneumonia. A pneumonia that does not rapidly clear with antibiotics is cause for concern for lung cancer, especially in patients with a tobacco history.
