Dr. Jyotsna Joshi and Dr. Unnati Desai summarise the main advances and guideline updates that affected Pulmonology and Respiratory Medicine practice this year.

The year 2019 has seen many advances and updates in the diverse field of Pulmonology. This article aims to summarise the important guidelines advances made this year.

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Asthma

The Global Initiative for Asthma (GINA) 2019 recommended the following changes:

1. For safety purposes, GINA no longer recommends treatment with short acting beta2-agonist (SABA) alone.
2. Patients should receive symptom-driven or daily low dose inhaled corticosteroid s (ICS) containing controller therapy for example budesonide and long acting beta2-agonists (LABA) like formoterol.

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Chronic Obstructive Pulmonary Disease (COPD)

The GOLD 2019 guideline update recommended a LABA/ICS combination for initial treatment in patients with an eosinophil count greater than 300 cells/µL or those with a history of asthma and COPD. Patients who develop exacerbations while on a LAMA/LABA may be escalated to a LABA/LAMA/ICS. A single inhaler may be used for the same.

Preventive measures in COPD included vaccinations and smoking cessation. The yearly influenza vaccine and the PPSV23 and PCV13 pneumococcal vaccines are recommended in all patients with COPD. PPSV23 is recommended for patients aged 19 to 64 years, and PCV13 is recommended for patients aged 65 years and older, administered at least 1 year after PPSV23.

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Interstitial Lung Disease (ILD)

The American Thoracic Society ATS/ European Respiratory Socity ERS 2018 Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) guidelines recommended the following:

1. For adult patients with newly detected ILD of apparently unknown cause, who are clinically suspected of having IPF- Take a detailed history of both medication use and environmental exposures and serological testing for connective tissue disease to exclude potential causes of ILD [motherhood statement].
2. For patients with newly detected ILD of apparently unknown cause who are clinically suspected of having IPF and have an HRCT pattern of probable UIP, indeterminate for UIP, or an alternative diagnosis- It suggests cellular analysis of their BAL fluid or surgical lung biopsy [conditional recommendation, very low quality of evidence]. The panel made no recommendation for or against transbronchial lung biopsy (TBBx) or lung cryobiopsy.
3. For patients with newly detected ILD of apparently unknown cause who are clinically suspected of having IPF and have an HRCT pattern of UIP-
   • It suggests NOT performing cellular analysis of their BAL fluid [conditional recommendation, very low quality of evidence]
   • It recommends NOT performing SLB or TBBx or lung cryobiopsy [strong recommendation, very low quality of evidence]
4. For patients with newly detected ILD of apparently unknown cause who are clinically suspected of having IPF-
   • It suggests multidisciplinary discussion (MDD) for diagnostic decision-making [conditional recommendation, very low quality of evidence]
   • It recommends NOT measuring any biological markers in serum or BAL for the purpose of distinguishing IPF from other ILDs [strong recommendation, very low quality of evidence]

The US Food and Drug Administration (FDA) approved nintedanib for slowing the rate of decline in pulmonary function in adults with systemic sclerosis–associated interstitial lung disease (SSc-ILD) in 2019.

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Lung cancer

The horizon on lung cancer drug developments and mutations sees a humongous amount of trial data and literature updates every year. But the developments still do not meet recommendations to be updated in a guideline. This year saw an update on malignant pleural effusions.

The ATS/ERS 2018 management of pleural effusions guidelines recommended the following:

1. In patients with known or suspected malignant pleural effusion (MPE), it suggested that ultrasound imaging be used to guide pleural interventions.
2. In patients with known or suspected MPE who are asymptomatic, it suggested that therapeutic pleural interventions should not be performed.
3. In patients with symptomatic MPE, it suggested large-volume thoracentesis if it is uncertain whether the patient’s symptoms are related to the effusion and/or if the lung is expandable (the latter if pleurodesis is contemplated), to assess lung expansion.
4. In patients with symptomatic MPE with known (or likely) suspected expandable lung, and no prior definitive therapy, it suggested that either an indwelling pleural catheter (IPC) or chemical pleurodesis be used as first-line definitive pleural intervention for management of dyspnoea.
5. In patients with symptomatic MPE and expandable lung undergoing talc pleurodesis, it suggested the use of either talc poudrage or talc slurry.
6. In patients with symptomatic malignant pleural effusions with non-expandable lung, failed pleurodesis, or loculated effusion, it suggested the use of IPCs over chemical pleurodesis.
7. In patients with IPC-associated infections, treating through the infection without catheter removal is usually adequate. It suggested catheter removal if the infection fails to improve.

The year also gave us evidence that palliative care initiation within a year of an advanced lung cancer diagnosis was associated with increases in survival and should be considered a complementary approach to disease-modifying therapy.

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Pneumothorax

A review on literature updates on pneumothorax suggested that:

1. Current guidelines recommend needle aspiration prior to chest drain insertion for primary spontaneous pneumothorax (PSP), but that secondary spontaneous pneumothorax (SSP) should be treated with chest drain.
2. Ambulatory management should be encouraged.
3. Clinicians should be vigilant for PSP being the first manifestation of a systemic disease, and should have a low threshold for onward referral and CT scan evaluation of the lung parenchyma.
4. Future studies should utilise risk stratification by clinical and radiological parameters (e.g. HRCT scanning and digital air leak monitoring) to predict short- and long-term outcomes, and hence personalise management.
5. The focus of treatment should move to outpatient management whenever possible, especially when no intervention to prevent recurrence is performed.

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Pulmonary Hypertension

The 6th World Symposium on Pulmonary Hypertension (WSPH) was conducted to review the most relevant clinical and scientific advances in the field. Based on careful review and discussions by members of the different task forces which were available in 2019, the following changes were suggested:

Major revision defined 3 haemodynamic profiles of pulmonary hypertension (PH):

• isolated pre-capillary PH
• combined pre- and post-capillary PH
• isolated post-capillary PH on the basis of mean pulmonary arterial pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance

New genes were added to the list of genetic markers associated with pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease.

The use of risk stratification tools was encouraged as a strategy to reduce one-year mortality risk in PAH patients through early implementation of PAH therapies.

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Pulmonary Thromboembolism

In 2019, the European Society of Cardiology (ESC) with the ERS updated guidelines for the diagnosis and management of acute pulmonary embolism. The main new recommendations in 2019 were:

Diagnosis:

• D-dimer test should use an age-adjusted cut-off or adapted to clinical probability, as an alternative to the fixed cut-off level. If a positive proximal CUS is used to confirm PE, risk assessment should be considered to guide management
• V/Q SPECT may be considered for PE diagnosis

Risk assessment: Assessment of the RV by imaging or laboratory biomarkers should be considered, even in the presence of a low PESI or a sPESI of 0. Validated scores combining clinical, imaging, and laboratory prognostic factors may be considered to further stratify PE severity.

Treatment in the acute phase: When oral anticoagulation is initiated in a patient with PE who is eligible for a novel oral anticoagulant (NOAC- apixaban, dabigatran, edoxaban, or rivaroxaban), an NOAC is the recommended form of anticoagulant treatment. Set-up of multidisciplinary teams for management of high-risk and selected cases of intermediate-risk PE should be considered, depending on the resources and expertise available in each hospital. Extracorporeal membrane oxygenation (ECMO) may be considered, in combination with surgical embolectomy or catheter-directed treatment, in refractory circulatory collapse or cardiac arrest.

Chronic treatment and prevention of recurrence:

• Indefinite treatment with a VKA is recommended for patients with antiphospholipid antibody syndrome
• Extended anticoagulation should be considered for patients with no identifiable risk factor for the index PE event
• Extended anticoagulation should be considered for patients with a persistent risk factor other than antiphospholipid antibody syndrome
• Extended anticoagulation should be considered for patients with a minor transient/reversible risk factor for the index PE event
• A reduced dose of apixaban or rivaroxaban should be considered after the first 6 months

PE in cancer: Edoxaban or rivaroxaban should be considered as an alternative to LMWH, with the exception of patients with gastrointestinal cancer.

PE in pregnancy:

• Amniotic fluid embolism should be considered in a pregnant or post-partum woman, with unexplained haemodynamic instability or respiratory deterioration, and disseminated intravascular coagulation
• Thrombolysis or surgical embolectomy should be considered for pregnant women with high-risk PE
• NOACs are not recommended during pregnancy or lactation

Post-PE care and long-term sequelae:

• Routine clinical evaluation is recommended 3-6 months after acute PE
• An integrated model of care is recommended after acute PE to ensure optimal transition from hospital to ambulatory care
• It is recommended that symptomatic patients with mismatched perfusion defects on a V/Q scan >3 months after acute PE are referred to a pulmonary hypertension/CTEPH expert centre, taking into account the results of echocardiography, natriuretic peptide, and/or cardiopulmonary exercise testing

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Sleep

The year saw an update in an important clinical aspect of sleep-disordered breathing. The guideline for evaluation and management for obesity hypoventilation syndrome (OHS), published by ATS in 2019 recommended:

1. For obese patients with sleep-disordered breathing with a high pretest probability of having OHS, partial pressure of carbon dioxide (PaCO2) rather than serum bicarbonate or oxygen saturation (SpO2) be measured to diagnose OHS.
2. For patients with low to moderate probability of having OHS (<20%), serum bicarbonate level should be used to decide when to measure PaCO2:
   • In patients with serum bicarbonate <27 mmol/L, clinicians might forego measuring PaCO2, as the diagnosis of OHS in them is very unlikely
   • In patients with serum bicarbonate >27 mmol/L, clinicians might need to measure PaCO2 to confirm or rule out the diagnosis of OHS
3. Clinicians should avoid using SpO2 during wakefulness to decide when to measure PaCO2 in patients suspected of having OHS [conditional recommendation, very low level of certainty in the evidence].
4. For stable ambulatory patients diagnosed with OHS, treatment with PAP during sleep is suggested [conditional recommendation, very low level of certainty in the evidence].
5. For stable ambulatory patients diagnosed with OHS and concomitant severe OSA (apnoea–hypopnoea index>30 events/h), continuous positive airway pressure (CPAP) should be the first-line treatment rather than non-invasive ventilation (NIV); [conditional recommendation, very low level of certainty in the evidence].
6. The hospitalised patients with respiratory failure suspected of having OHS could be started on NIV therapy before being discharged from the hospital, until they undergo outpatient workup and titration of positive airway pressure (PAP) therapy in the sleep laboratory, ideally within the first 3 months after hospital discharge [conditional recommendation, very low level of certainty in the evidence].
7. For patients with OHS, weight-loss interventions that produce sustained weight loss of 25 to 30% of actual body weight must be used. This level of weight loss is most likely required to achieve resolution of hypoventilation [conditional recommendation, very low level of certainty in the evidence].

In addition the The US Food and Drug Administration (FDA) has approved pitolisant for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy.

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Spirometry

An update of the 2005 American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines for the standardisation of spirometry published in 2019 recommended the following:

1. A new list of relative contraindications was added- Spirometers are now required to meet International Organization for Standardization (ISO) 26782 standards, but with a maximum permissible accuracy error of +2.5%.
2. Device quality assurance procedures were updated.
3. Operator training as well as attainment and maintenance of competency were addressed.
4. The list of activities that patients should avoid before testing was updated.
5. There was a focus on the use of devices that measure both expiration and inspiration.
6. Maneuver acceptability and repeatability criteria were updated.
7. The end of forced expiration (EOFE) was redefined.
8. Requirements for spirometry systems to provide uniform cues and feedback to the operator were added.
9. New withholding times for bronchodilators before bronchodilator responsiveness testing were developed.
10. A new grading system for assessment of spirometry quality was developed.
11. Standardised operator feedback options that promote synoptic reporting were developed.

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Interventional Pulmonology

In 2019, exhaustive guidelines for diagnostic flexible bronchoscopy in adults were published jointly by the Indian Chest Society/National College of Chest Physicians (I)/Indian Association for Bronchology. This was a comprehensive, evidence‑based guideline, including the key aspects of bronchoscopy to serve as a reference document for bronchoscopists, especially in the Indian context. Topics covered in the guideline were:

• Setting up of a bronchoscopy unit
• Indications, complications, and contraindications of flexible bronchoscopy
• Patient monitoring
• Sedation, premedication, and anaesthesia for flexible bronchoscopy
• Diagnostic procedures during flexible bronchoscopy: Bronchial washings (BW), bronchial brushings (BB), bronchoalveolar lavage (BAL), transbronchial needle aspiration (TBNA), endobronchial biopsy (EBB), and transbronchial lung biopsy (TBLB)
• Equipment disinfection and staff safety
• Flexible bronchoscopy in the ICU
• Training in flexible bronchoscopy

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Community Acquired Pneumonia

The American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) published its revised guideline in 2019 for adults who were not immunocompromised. It had the following changes:

1. Sputum and blood culture recommended for severely ill patients and for all inpatients who have received empiric treatment for Methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa.
2. Macrolide monotherapy now conditionally recommended for outpatients on the basis of resistance levels.
3. Recommendation against the use of serum procalcitonin for distinguishing between bacterial and viral infection and whether or not a patient requires antibacterial therapy.
4. Recommendation against the use of corticosteroids in patients with community-acquired pneumonia, but consideration for using them in patients with refractory septic shock.
5. Abandoning the use of the healthcare-associated pneumonia category. Rather, focus on using local epidemiology data and validated risk factors to determine whether the patient needs coverage for MRSA or Pseudomonas aeruginosa and an increased emphasis on de-escalating treatment if culture results are negative.
6. Recommendation of both β-Lactam/macrolide and β-lactam/fluoroquinolone combinations for treatment but, stronger evidence favouring a β-lactam/macrolide combination.
7. Routine use of follow-up chest imaging not recommended; but patients who are eligible for lung cancer screening to undergo chest imaging as clinically indicated.

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Tuberculosis

Drug resistant tuberculosis management has undergone a paradigm shift. The WHO in early 2019 released its consolidated guidelines on drug-resistant tuberculosis treatment. The major changes included use of the standardised shorter regimen in MDR-TB/RR-TB satisfying certain criteria, reclassification of drugs and use of newer drugs to formulate longer individualised treatment regimens in those ineligible for shorter regimen.

A recent December 2019 rapid communication from the WHO added the following suggestions:

1. All patients with MDR/RR-TB, including those with additional resistance to fluoroquinolones, stand to benefit from effective all-oral treatment regimens, either shorter or longer, implemented under programmatic conditions.
2. MDR/RR-TB patients with extensive TB disease, severe forms of extrapulmonary TB, those with resistance to fluoroquinolones or who have been exposed to treatment with second-line drugs will benefit from an individualised longer regimen designed using the WHO priority grouping of medicines recommended in 2018.
3. For MDR/RR-TB patients without previous exposure to second-line treatment (including bedaquiline), without fluoroquinolone resistance and no extensive TB disease or severe extrapulmonary TB, the preferred treatment option is a shorter, all-oral, bedaquiline-containing regimen. In this group of patients, national TB programmes are advised to phase out use of the injectable-containing shorter regimen.
4. Access to rapid drug susceptibility testing, especially for ruling out fluoroquinolone resistance, is required before starting the shorter, all-oral, bedaquiline-containing MDR-TB regimen.
5. In settings with a high probability of, or patients with confirmed resistance to other medicines in the regimen, further modifications of the shorter, all-oral, bedaquiline-containing regimen using priority grouping of second-line TB medicines may be implemented. However, the efficacy, safety and tolerability of such modifications to regimens <12 months are unknown and should therefore be evaluated under operational research conditions.
6. The bedaquiline, pretomanid and linezolid (BPaL) regimen may be used under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB) who have not had previous exposure to bedaquiline and linezolid (defined as less than two weeks). This regimen may not be considered for programmatic use worldwide until additional evidence on efficacy and safety has been generated. However, in individual patients for whom design of an effective regimen based on existing recommendations is not possible, BPal regimen may be considered as a last resort under prevailing ethical standards.
7. Decisions on appropriate regimens should be made according to patient preference and clinical judgement, also considering the results of susceptibility testing, patient treatment history, and severity and site of the disease.
8. All treatment should be delivered under WHO-recommended standards, including patient-centered care and support, informed consent where necessary, principles of good clinical practice, active drug safety monitoring and management, and regular patient monitoring to assess regimen effectiveness.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author, Dr. Jyotsna Joshi is a Former Professor of Pulmonary Medicine and a Consultant Pulmonologist at a reputed Mumbai hospital.