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Airways Disorders
Inhaled corticosteroids in COPD: When to hold and when to fold
The 2017 GOLD guidelines reiterated that inhaled corticosteroids (ICS) be reserved for COPD patients with continued symptoms and exacerbations, despite use of long-acting beta-agonists (LABAs) and long-acting muscarinic agents (LAMAs). ICS are appropriate in approximately 40% of patients; however, prescribing rates can exceed 80% (Yawn et al. 2016; Primary Care Respir J. 26:16068).
Recent literature has begun to define the appropriate use of ICS in COPD. ICS/LABA combinations improve outcomes in patients with moderate to very severe COPD with frequent exacerbations. However, ICS/LABA may not further diminish exacerbation risk compared with those treated with a LABA/LAMA combination (Wedzicha et al., N Engl J Med. 2016;374:2222).
While the addition of LAMA to an ICS/LABA combination (triple therapy) improved lung function and decreased exacerbation risk, the addition of ICS to LABA/LAMA combination did not decrease exacerbations (GOLD Guidelines 2017). It has been suggested that those with asthma-COPD overlap identified by sputum eosinophilia represent ideal candidates for ICS therapy (GINA Guideline 2016).
ICS use in COPD increases pneumonia risk. The risk was highest in the very group for which guidelines recommend its use – those with a FEV1 less than 50% of predicted or with prior COPD exacerbation (Ernst et al. Eur Respir J. 2015;45:525).
ICS may be safely withdrawn in low-risk patients (FEV1 less than 50% predicted and no exacerbations in the previous year [Yawn et al.]).
In a trial comparing patients with severe COPD (FEV1 less than 50%) on continued LAMA/LABA/ICS triple therapy vs LAMA/LABA with ICS withdrawal, the risk of moderate or severe exacerbations at 52 weeks was not increased (Magnussen et al. N Engl J Med. 2014;371:1285).
Conclusions
Based on the 2017 GOLD guidelines:
• Monotherapy with ICS is not recommended in COPD.
• In patients with continued respiratory-related symptoms without exacerbations (GOLD group B), LAMA or LABA or LAMA/LABA combination is recommended. There is no recommendation for ICS in this group.
• In patients with frequent exacerbations (GOLD groups C and D), LAMA/LABA combinations are preferred to LABA/ICS because of superior effectiveness (especially in Group D) and the increased pneumonia risk with ICS. Escalation to triple therapy can be considered if there are continued exacerbations.
Allen Blaivas, DO, FCCP
Steering Committee Member
Navitha Ramesh, MD, MBBS
Fellow-in-Training Member
Home-Based Mechanical Ventilation and Neuromuscular Disease
Advances in neuromuscular disease
Spinal muscular atrophy (SMA) type 1 is the most deadly inherited disease among infants, with most infants dying by 1 to 2 years of age without supportive therapies, such as assisted ventilation. It is caused by homozygous deletions or mutations in the survival motor neuron 1 (SMN1) gene. Disease severity varies in part depending on the number of backup SMN2 gene copies that can produce some functional SMN protein (Arnold et al. Muscle Nerve. 2015;51[2]:157).
Recent developments of disease-modifying agents are giving hope to individuals with SMA and their families. Nusinersen (an antisense oligonucleotide) is an intrathecal medication that increases the production of functional SMN protein by increasing SMN2 exon 7 transcription (Chiriboga et al. Neurology. 2016;86[10]:890).
A recent open-label clinical trial by Finkel et al. (Lancet. 2017;388[10063]:3017) showed a “promising clinical response” that altered the natural history of disease progression. Most infants treated with multiple intrathecal doses of nusinersen had incremental improvement in their motor milestones and motor function (P = .008), as well as improved survival and/or avoidance of ventilation (P = .0014).
Moreover, the study found significant uptake of nusinersen by the motor neuron throughout the spinal cord and other neurons throughout the CNS. It appeared to be well tolerated. Disease-modifying medications may soon become “game changers” in many neuromuscular conditions.
However, a significant concern is the expected prohibitive cost both of a rare-disease-modifying therapy and of administrating intrathecal medications to fragile infants. As such, those obstacles will need to be overcome as neuromuscular clinics, hospitals, and payers start planning for the coming advances that our patients will be expecting.
Ahlam Mazi, MBBS
Fellow-in-Training Member
Interstitial and Diffuse Lung Disease
New advancements in predictive risk factors of IPF
In the last few years, many predictive risk factors were studied in clinical trials monitoring idiopathic pulmonary fibrosis (IPF), such as forced vital capacity and diffuse lung capacity for carbon monoxide (King TE Jr, et al. ASCEND Study Group. N Engl J Med. 2014;18;371[12]:1172; Richeldi L, et al. INPULSIS Trial Investigators. N Engl J Med. 2015;20;373[8]:782; Ley B, et al. Am J Respir Crit Care Med. 2016;15;194[6]:711).
Recent data that have not yet been published by Carbone et al evaluate the prognostic value of the New York Heart Association index (NYHA) compared with high resolution CT scan, somatostatin receptor scintigraphy (octreoscan), and echocardiography in a study population of 128 patients suffering from IPF (61% male subjects), nonspecific interstitial pneumonia, and granulomatous lung diseases (alveolitis, sarcoidosis, granulomatosis with polyangiitis). All patients were confirmed histologically.
The NYHA came out as a reliable prognostic factor in each setting. In fact, the log-rank test showed significant differences among NYHA categories, as cases included with disease showed the worst survival rate while no death cases were observed when NYHA was negative.
Moreover, the prognostic value of NYHA was confirmed by multivariate analysis, where the survival rate results were significantly different among patients with level 7 after adjustment for other variables included in the model.
Furthermore, the prognostic value of the NYHA index was once again confirmed when the analysis was limited to cases with the histological pattern of IPF (usual interstitial pneumonia).
The authors, therefore, strongly recommend utilization of the NYHA index as a prognostic factor of IPF as well as granulomatous lung diseases.
Roberto Carbone, MD, FCCP
Steering Committee Member
A. Monselise, MD, PhD
NetWork Nonmember
