Interstitial lung disease Check

Question 1

Which occupations are at risk of asbestos exposure

Answer 1

‘manufacture of asbestos products, asbestos mining and milling, construction trades (including insulators, sheet metal workers, electricians, plumbers, pipefitters, and carpenters), power plant workers, boilermakers, and shipyard workers’.[13]

Question 2

Spirometry demonstrates Reduced FVC and Decreased TLC?

Vs Reduced FVC and Increased TLC

Answer 2

Both reduced = true restrictive

Reduced FVC and increased TLC = hyperinflation? gastrapping?

Question 3

What does Decreased DLCO suggest?

What about decreased DL/VA (Diffusion capacity)?

Answer 3

DLCO decreased means GAS TRANSFER IS REDUCED

IF DL/VA is decreased - it means that reduction in gas transfer cannot be fully explained by a reduction in alveolar volume

Question 4

What is a pleural plaque

Answer 4

THickiening of pleura

usally asymptomatic and benign

ALMOST universally caused by asbestos exposure - good indicator of presence of exposure but NOT good indicator of how much exposure

Question 5

Do pleural plaques need further Ix

Answer 5

Usually not in isolation if asymptomatic

BUT can indicate a need for monitoring of lung function decline or future development of asbestosis

CAN Sometime develop a small area of collapse next to the plaque called a ROUND ATELECTASIS (benign)

Question 6

What happens if a patient with asbestos exposure develops pleural effusion

Answer 6

needs thorough investigation for asbestosis and mesothelioma

usually blood stained

can recur in 32%

time to resolution is usually 4 mnths

Question 7

What is asbestosis

Answer 7

Asbestosis is a parenchymal lung disease characterised by interstitial pneumonitis and fibrosis, caused by inhalation of asbestos.

Asbestosis is a chronic, usually slowly progressive condition that causes progressive dyspnoea and premature death. Asbestosis is a risk factor for the development of lung cancer. Smoking increases the progression of asbestosis and is a multiplicative risk factor for lung cancer.

Question 8

What is the pathology on HRCT with asbestosis

Answer 8

On high-resolution computed tomography (HRCT), this often presents as honeycombing and reticulation with a lower lobe and subpleural predominance, often representing a usual interstitial pneumonia pattern.[13,17]

However, more recently a post-mortem study of asbestos-exposed workers has demonstrated that the pathological changes observed were more in keeping with a fibrotic non-specific interstitial pneumonia pattern

Question 9

How long does asbestosis take to become symptomatic

Answer 9

sbestosis usually takes 20–30 years from initial exposure to become symptomatic but can be shorter with increased intensity of asbestosis exposure

Question 10

What is mesothelioma

Answer 10

Mesothelioma is a malignancy that arises in the pleura, peritoneum, pericardium or tunica vaginalis and is highly associated with asbestos exposure.

Question 11

How is asbestos exposure related to NSLC?

Answer 11

Asbestos exposure is a risk factor for the development of non–small cell lung cancer. In patients who have a history of cigarette smoking, the risk of lung cancer is multiplicative.[19]

Question 12

How would an asymptomatic worker with asbestos exposure or pleural plaque be monitored

Answer 12

baseline clinical assessment, lung function testing and CXR. If the worker is at significant risk of developing asbestos-related pathology, periodic assessment including lung function tests and CXR every 3–5 years would also be reasonable.

Question 13

What is the differential for a patient with asbestos exposure and smoking who has an HRCT which shows usual interstitial pneumonia

Answer 13

Asbestosis

Idiopathic pulmonary fibrosis

Important distinciton as 1) IPF much more rapid progression and 2) IPF they can access anti fibrotic therapy on the PBS whereas asbestosis they cant

Question 14

Management of Asbestosis

Answer 14

There are currently no specific therapies for asbestosis; treatment is supportive:

1. focusing on smoking cessation,
2. immunisation for pneumococcal and influenza,
3. supplemental oxygen if required,
4. and avoidance of further hazardous inhalational material.
5. In addition, patient education,
6. pulmonary rehabilitation
7. and direction to a support group may be helpful.
8. Patients may also be entitled to compensation for dust exposure–related disease.
9. Finally, ongoing surveillance for progressive disease or development of malignancy is warranted, especially if the patient has a smoking history.

Question 15

Risk of malignancy in smokers with asbestos

Answer 15

1. Asbestos exposure is an established risk factor for lung cancer,
2. and this risk is multiplicative in smokers.
3. Smoking and asbestos exposure are also established risk factors for mesothelioma.

Question 16

What is the impact of pleural effusion on a patient with asbestosis

Answer 16

1. A pleural effusion will further compromise Jakub’s pulmonary function.
2. He is likely to require a diagnostic and therapeutic thoracocentesis.
3. A pleural effusion in a patient with asbestos exposure and a history of smoking raises serious concerns for possible mesothelioma or lung cancer.
4. Nevertheless, the differential diagnosis for pleural effusion is wide, and this needs to be evaluated.

Question 17

A patient with mesothelioma decides against treatment - what would your management plan be

Answer 17

ongoing supportive care including:

1. emotional support,
2. education,
3. pain relief
4. and consideration of home oxygen (if he has quit smoking).
5. If he has a persistent large pleural effusion, Jakub may obtain symptom relief with placement of an indwelling pleural catheter by the local thoracic service.
6. He may also require engagement with community palliative service for additional supports.
7. It would be worth preparing an advanced healthcare directive.
8. Finally, Jakub should be advised that he may be eligible for compensation and should get in touch with an appropriate support group such as Lung Foundation Australia or the Asbestos Diseases Society of Australia to consider his options.

Question 18

Causes of restrictive pattern on spirometry

Answer 18

lung diseases such as ILD and pneumonia

pleural disease, such as pleura effusion or diffuse pleural thickening

disease of the chest wall or movement such as neuromuscular disorders, diaphragm palsy, kyphoscoliosis or obesity.

Question 20

What are the causes of ILD

Answer 20

Environmental causes – consider work exposures (eg asbestos or dust) as well as home or hobby exposures including keeping birds, mould in the house or home brewing. The patient does not have to be directly exposed; aviaries next door or in the vicinity or a habit of regularly feeding wild birds can be sufficient to cause lung disease. The list of environmental causes of lung fibrosis is legion, and even in specialist centres approximately 25% of cases thought to be due to an environmental trigger never have that trigger identified.[22]

Drugs – hundreds of medications have been associated with lung fibrosis, including chemotherapeutic agents, amiodarone and nitrofurantoin.[23] If you are concerned about a medication potentially causing lung disease, it can be looked up on Pneumotox, the drug-induced respiratory disease website (www.pneumotox.com).

Connective tissue disease – all the connective tissue diseases can cause pulmonary fibrosis.[24] Lung fibrosis can predate a formal diagnosis of connective tissue disease, so it is worth asking some broad screening questions about joint and skin disease.

Question 21

Examination findings in ILD

Answer 21

The clinical examination in patients with ILD can be unremarkable. Inspiratory crackles, most often bibasal, are often the only abnormal finding (THAT DO NOT CLEAR WITH COUGHING). Patients are often not hypoxic or visibly breathless unless the disease is advanced. Where the patient has a connective tissue associated–ILD, features of the systemic illness may be apparent (such as sclerodactyly, telangiectasia, Raynauds, arthritis). Clubbing is a useful clue; however, it is usually only seen in advanced cases, so its absence does not make the diagnosis less likely.[26]

Question 22

What tests would a specialist order for investigation of ILD

Answer 22

auto-antibody screen – antinuclear antibody (ANA), extractable nuclear antigen (ENA), angiotensin-converting enzyme (ACE), antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), double-stranded DNA (dsDNA), and if appropriate, myositis screen. These tests would usually only be done in a specialist setting following an initial assessment and possibly a rheumatology consultation.

Question 23

How does acute hypersensitivity pneumonitis present

Answer 23

n the acute forms, patients present abruptly with a flu-like illness tightly associated with a significant and identifiable exposure to a known hypersensitivity antigen. They have prominent airway symptoms such as cough and dyspnea, and potentially sputum, wheeze and upper airway symptoms. They are often constitutionally unwell with fatigue and fever. Provided the patient is withdrawn completely from exposure, the illness can be self-limiting quite quickly (eg within a day or two). If chest imaging is performed, there is often an upper lobe predominance of centrilobular nodules (or haziness on a CXR). The illness can easily be confused with a respiratory tract infection, except for the clear exposure relationship with a hypersensitivity antigen in a previously well person.

Question 24

How does a chronic hypersensitivty pneumonitis present?

Answer 24

Chronic hypersensitivity pneumonitis is more insidious in its onset.

Patients tend not to have prominent constitutional features or be febrile, but present with increasing dyspnoea and sometimes cough. It is possible, as in Bob’s case, for symptoms to worsen after a period of exposure and then subside somewhat but never completely resolve, only to slowly worsen over time. The exposure can be more chronic in nature – for example, a_n avian household pet, mould in the house, standing water with fungus colonisation, regular gardening using mulches/compost, occupational exposures such as yeasts, moulds (in hay/farms or office buildings), flour and so on._ The symptoms are not always obviously related to an exposure, so patients may be unaware of the offending antigen. Bob’s repeated exposure while working in the loft and potentially chronic low-level inhalational exposure from simply living in the house will have been sufficient to cause disease over many months. Patients with chronic hypersensitivity pneumonitis can develop fibrosis over time; if severe, this can potentially lead to respiratory failure and death.

Clinical features considered most relevant for diagnosis of chronic hypersensitivity pneumonitis include a history of environmental exposure, with clinical improvement on antigen avoidance; relevant HRCT and histopathological changes; as well as multidisciplinary team agreement regarding the diagnosis.

Question 25

Is identification of antigen needed for diagnosis of chronic hypersenstivity pneumonitis

Answer 25

Identification of the antigen is useful for diagnosis and management. However, up to 25% of chronic hypersensitivity pneumonitis diagnoses are made in the absence of an identifiable hypersensitivity antigen

Question 26

Management of chronic hypersensitivity pneumonitis

Answer 26

**antigen avoidance** – Bob must forego cleaning his loft and ask a professional to do it; the house should also be professionally cleaned. In some cases, the impact of this can be profound, such as necessitating a change in employment or living situation. **pharmacotherapy** – Steroids are commonly required for severe or progressive disease, or where antigen avoidance is incomplete or insufficient to resolve the disease. Treatment may be for months to years and long-term survival benefit has not been demonstrated.[22,25,26] Other immunosuppressive therapies are occasionally used, though to date there is only a very limited evidence base for this. **supportive and preventive care** – This may include smoking cessation, immunisation for pneumococcal and influenza, avoidance of further hazardous inhalational material, and supplemental oxygen if required. **multidisciplinary team involvement** is recommended, and may include condition-specific roles such as an occupational physician or environmental technologist. Given Bob’s relatively young age, close specialist follow-up is indicated. If his disease progresses, a transplant referral may be considered.

Question 27

Prognosis in chronic hypersensitivity pneumonitis

Answer 27

29% mortality at 5 years. Can develop pulm fibrosis. Can also have some resolution of symptoms with antigen avoidance and steroids/immunosupressant therapy and multidisciplinary management

Question 28

CLinical evaluation for sarcoidosis?

Answer 28

History (occupational and environmental exposure) Physical examination: crackles, lymphadenopathy, hepatosplenomegaly, polyarthritis, rash, uveitis, nerve palsies Posteroanterior chest X-ray Pulmonary function tests: spirometry, lung volumes and carbon monoxide diffusion capacity Blood test: full blood count, biochemistry – calcium, liver enzymes, creatinine, blood urea nitrogen Urine analysis Electrocardiography Ophthalmologic examination Quantiferon gold assay

Question 30

What is the value of measuring serum ACE in sarcoidosis

Answer 30

Serum ACE may be measured in blood and is used as an indicator of activity in sarcoidosis. ACE is produced by the epithelioid cells of the sarcoid granuloma and may correlate with granulomatous disease burden. Nonetheless, ACE may be normal in many patients with sarcoidosis and **elevated in other granulomatous diseases, lymphoma, human immunodeficiency virus, cirrhosis, diabetes, tuberculosis and hyperthyroidism,** tending to limit diagnostic accuracy. Furthermore, concentration may be falsely lowered in patients taking ACE inhibitor medication or those with COPD, hypothyroidism or cystic fibrosis.

Question 31

HOw is a diagnosis of sarcoidosis reached?

Answer 31

Diagnosis of sarcoidosis if usually made with the combination of:[30] compatible **clinical and radiological features** **exclusion of other causes** demonstration of **non-caseating granulomas on tissue biopsy.**

Question 32

DDx for bilateral symettrical hilar lymphadenopathy

Answer 32

SARCOIDOSIS Ddx The differential diagnosis for bilateral symmetric hilar adenopathy rarely includes lymphoma, but constitutional symptoms are usually present or develop shortly after presentation, and reticulonodular changes are typically absent.[28]

Question 33

What is the differential diagnosis for reticulo-nodularity

Answer 33

The differential diagnosis for reticulonodularity includes **sarcoidosis, silicosis, tuberculosis and lymphangitis carcinomatosis**

Question 34

Role of specialists in sarcoid

Answer 34

Provide histological confirmation of the disease. (biopsy/ may use PET scanning to find granulmoa and/or endobronchial ultrasound with transbronchial needle aspiration when mediastinal and hilar lymph nodes are involved) Evaluate the extent and severity of organ involvement. Assess whether the disease is likely to progress. Determine the role of treatment.

Question 35

How is pulmonary sarcoid treated

Answer 35

Oral corticosteroid therapy for a minimum of twelve months second line - dmards azathioprine, methotrexate or biologics/immune suppresants - infliximab, cyclophosphamide,

Question 36

How would you monitor a patient on long term steroid therapy?

Answer 36

1. Monitor **Weight, BP, Lipids, glucose, UEC** 2. **Yearly eye review** for cataract formation and glaucoma 3. **Bone density at baseline and then yearly for anyone taking more than 5mg daily**. (Lower threshold for antiresorptive therapy) 4. Those on maintenance less than 15mg a day should have their dose transiently increased during times of acute intercurrent illness or stress until full recovery (to prevent adrenal crisis)

Question 37

What happens if a patient with sarcoid commences vitamin D or calcium therapy for osteoporosis prevention?

Answer 37

Special care must be used if vitamin D or calcium is prescribed for osteoporosis prevention or treatment, because **sarcoidosis may cause hypercalciuria and hypercalcemia** _by increased endogenous vitamin D._ ***_Serum calcium and 24-hour urinary calcium should be monitored before and one month after commencing therapy._***

Question 38

Monitoring of patients with Sarcoid Prognosis

Answer 38

6-12 monthly with CXR and Pulm function tests and clinical assessment. Prognosis depends on the staging.

Question 39

Two main causes of breathlessness in a patient with systemic sclerosis (Scleroderma)

Answer 39

1. Interstitial lung disease 2. Pulmonary artery hypertension 3. Anaemia from bleeding telangiectasiae in GI tract 4. Cardiac arrhythmias/fibrosis

Question 40

What respiratory screening should occur for patients with systemic sclerosis?

Answer 40

all patients with known or suspected SSc should undergo **TTE and spirometry (pulmonary function tests including FVC and DLCO), ideally once each year** ## Footnote **If on screening SPAP is greater than or equal to 40** **AND DLCO is less than or equal to 50 then right heart catheter**

Question 41

When should a patient with SOB and Systemic sclerosis be referred

Answer 41

new onset of dyspnoea or reduced exercise capacity in the absence of known ILD, PAH or other causes of reduced exercise capacity such as SSc-related myopathy or heart disease decline in exercise capacity to a worse functional class in the setting of known ILD or cardiac disease

Question 42

When can DLCO be low

Answer 42

Both in parenchymal lung disease (ILD, Emphysema) AND Pulmonary arterial hypertension

Question 43

What therapies are used for ILD in SSc

Answer 43

**Cyclophosphamide** **Mycophenolate** Contraindications are: **Pregnancy, lactation, systemic infections** Can have flu and pneumovax after but must avoid live attenuated vaccines Sideffects of both are: **Reduced fertility, bone marrow suppression, lymphoma risk** IN CYC (only) - **haemorrhagic cystitis** can occur

Question 44

CYC and MMF in preg

Answer 44

avoid CYC in preg as can be teratogenic Also Mycophenolate should be switched to Azathioprine in preg Both can reduce fertility. ILD itself can lead to difficulties in preg and pre term labour

Question 45

What history is suggestive of ILD? What examination findings?

Answer 45

Older age (median age: 66 years)[ Exertional dyspnoea (present in 90% of patients) Non-productive cough (present in \>70% of patients) Decreased exercise tolerance Weight loss Features suggestive of an underlying cause of ILD, including clinical features of **connective tissue disease, occupational and recreational causes and medication-related ILD** Risk factors including **family history and smoking history** Examination findings suggestive of ILD **Finger clubbing (**present in 30–50% of patients)[69] **Bibasilar crackles** (typically late inspiratory velcro-like fine crackles) **Hypoxia** on pulse oximetry Features of **cor pulmonale** (in advanced disease) including raised jugular venous pressure and ankle oedema

Question 46

What are the important investigations in a patient with suspected ILD

Answer 46

1. Formal Pulmonary function tests 2. HRCT 3. Six minute walk test with oximetry 4. Echocardiogram 5. Auto-antibody testing 6. Full blood count They then go on to have bronchoscopy +/- BAL and lung biopsy

Question 47

HOw does a six minute walk test help in ILD?

Answer 47

This is an assessment of the severity of the underlying ILD and may be important in identifying concomitant pulmonary hypertension. It is also important to assess regularly for requirement for supplemental oxygen.

Question 48

What are the features of Idiopathic pulm fibrosis on HRCT?

Answer 48

HRCT features suggestive of idiopathic pulmonary fibrosis (IPF) are well described as a specific pattern **(usual interstitial pneumonia [UIP]**). The features of UIP are clearly defined in the American Thoracic Society (ATS)/European Respiratory Society (ERS) 2018 diagnostic guidelines[1] and **include subpleural and basal predominant changes, heterogeneous distribution and honeycombing with or without traction bronchiectasis.**

Question 49

How does IPF differ to other ILD's

Answer 49

IPF is a disease of the lung interstitium that appears to arise from a **process of primary fibrosis**. This is unlike many other forms of ILD, where inflammation is the primary process, and fibrosis may occur in response. While immunosuppressive therapy has proven useful in some forms of ILD, for IPF it has been unhelpful or even detrimental.

Question 50

What are the antifibrotic drugs available for treatment of IPF?

Answer 50

antifibrotic agents **nintedanib and pirfenidone** are now recommended for the treatment of mild-to-moderate IPF in the updated multinational clinical practice guidelines[71] and are now available under the Pharmaceutical Benefits Scheme (PBS).

Question 51

Sideffects of pirfenidone

Answer 51

Pirfenidone is generally well tolerated with mostly mild adverse events being reported in a large analysis of safety outcomes. The most common side effects include **nausea (37.6%), diarrhoea (28.1%), dyspepsia (18.4%), vomiting (15.9%) and photosensitive rash (25%),** with nausea and rash being the most common symptoms leading to drug discontinuation.[74] It is particularly important to counsel patients in Australia and New Zealand about the **risk of photosensitivity and the importance of minimising direct sun exposure and using sun protection factor 50+ sunscreen.**

Question 52

Sideffects of Nintedanib

Answer 52

he most common side effect of nintedanib is **diarrhoea**, which occurs in approximately 60% of patients.[73] Diarrhoea is usually mild and can be managed with a low-fibre diet, good hydration and over-the-counter anti-diarrhoea agents. Diarrhoea results in cessation of nintedanib in \<5% of patients. Other common adverse events included **nausea, vomiting and decreased appetite,** occurring in 8–25% of patients. Specific advice on managing side effects is included in the latest version of the Australian Medicines Handbook. ## Footnote **INCREASED BLEEDING RISK - dont put them on anticoags**

Question 53

What about LFTs with anti fibrotic agents? how often do they need bloods?

Answer 53

Both pirfenidone and Nintedanib can cause derangement of LFTs There is a risk of liver function abnormalities occurring with both antifibrotic agents, and patients are required to have baseline blood tests **(full blood count, electrolytes and liver function), and to have these repeated monthly for the first six months, and every three months thereafte**

Question 54

Non pharmacological managmenet of patients with IPF (ILD)

Answer 54

1. **smoking cessation**, which is of particular relevance as smoking may reduce efficacy of antifibrotic therapy, and is a barrier to oxygen therapy 2. optimisation of **nutrition for overall health and transplant eligibility** 3. **vaccinations** against influenza and pneumococcus 4. early recognition and treatment of **respiratory infections** 5. assessment for and treatment of **comorbidities**, with particular consideration of coronary disease, lung cancer, gastro-oesophageal reflux, pulmonary embolism, pulmonary hypertension, emphysema, airways disease and obstructive sleep apnoea 6. **pulmonary rehabilitation,** which has been shown to lead to significant benefits in exercise capacity, symptoms and health-related quality of life, particularly earlier in the disease course;[76] early referral to a local pulmonary rehabilitation unit is encouraged 7. **consideration of the patient’s mental health;** depression and anxiety are common and often overlooked in patients with IPF, despite being associated with poorer quality of life and worse outcomes 8. **referral to a tertiary ILD unit for a multidisciplinary approach** involving respiratory physicians, nurse consultants, physiotherapists, dieticians and palliative care physicians; often patients with IPF are complex and benefit from a shared care approach with a general practitioner (GP), local respiratory physician and tertiary ILD centre 9. **monitoring of oxygen requirements at rest and on exercise,** and sometimes also overnight. Individual oxygen requirements will increase over time. In the more advanced stages, patients will qualify for supplemental oxygen through funded sources. Australian and New Zealand guidelines recommend oxygen therapy for patients with ILD who have resting hypoxaemia (partial pressure of arterial oxygen \<55 mmHg, or \<60 mmHg in the presence of hypoxic organ damage [including polycythaemia, pulmonary hypertension or right heart failure]). Guidelines are less specific with regard to intermittent ambulatory oxygen, which may be considered on an individual basis for those with exercise-induced desaturation where an improvement is seen in exercise capacity or dyspnoea, as assessed with a blinded trial of oxygen versus air during the six-minute walking test. Guidelines also recommend supplemental oxygen overnight for patients with ILD who desaturate below 88% for at least one third of total sleep time in the absence of concomitant sleep-disordered breathing.

Question 55

Disease Progression in ILD

Answer 55

It is important that patients are accurately informed and have **realistic** expectations. **Antifibrotic therapy** may slow disease progression; however, the disease will eventually progress in all patients despite therapy, and this needs to be addressed with the patient and their family support network. **Lung transplantation** is an important treatment option for those patients who have no absolute contraindication to transplantation. Early referral to a transplant centre is essential, as it is impossible to predict an individual patient’s disease trajectory. **Advanced care planning** is important and needs to be addressed with patients and their families. Early palliative or supportive care is recommended to help address symptoms of dyspnoea, cough and fatigue, which can be debilitating and independent of disease severity. There have been no proven therapies to reverse these symptoms in IPF.

Question 56

What has to occur in order for antifibrotic therapy to be put in place

Answer 56

Diagnosis must be confirmed at **specialist ILD MDM** before antifibrotics are considered, and a diagnosis of IPF at ILD MDM is necessary for antifibrotics to be prescribed on the PBS

Question 57

How are the ILD's subdivided?

Answer 57

ILD can be sub-classified into 1. **ILD of known association** related to an underlying **connective tissue disease** (eg systemic sclerosis or rheumatoid arthritis), **medications** (eg bleomycin, amiodarone, methotrexate and nitrofurantoin) and **occupational exposures** (eg asbestos and silica exposure). A detailed history to uncover such risk factors should be performed. 2. **Granulomatous lung disease,** including **sarcoidosis or hypersensitivity pneumonitis**, is the second broad group of ILD. Hypersensitivity pneumonitis may be acute, subacute or chronic. In cases of chronic hypersensitivity pneumonitis, it can be particularly difficult to distinguish from idiopathic ILD, and close review of potential antigen (usually organic such as birds, mould, rising damp) is recommended. 3. The **idiopathic interstitial pneumonia**s are the most complicated subgroup. Pragmatically, they should be considered as either **IPF** (the most common of this group) or **non-IPF** for treatment and prognostic purposes. 4. Finally, there is a **miscellaneous group of rare ILD.** It is important to recognise that even with the most comprehensive assessments, up to 10% of ILD may remain unclassifiable.

Question 58

Asymptomatic pleural plaque on CXR - further investigations?

Answer 58

Further investigations for asymptomatic patients are not routinely indicated for patients with pleural plaques in isolation.