Oxygen therapy in patients with COPD with moderate desaturation

Two landmark trials from the early 1980s demonstrated survival benefit with long-term oxygen therapy (LTOT) in patients with COPD with severe resting hypoxemia [Sao₂ less than 89%; (Nocturnal Oxygen Therapy Trial Group. Ann Intern Med. 1980;93[3]:391) or Pao₂ 40-60 mm Hg and cor pulmonale (Report of the Medical Research Council Working Party. Lancet. 1981;1[8222]:681).

The potential benefits of LTOT in COPD with mild-moderate hypoxemia have not been clearly established. The LOTT trial (The Long-Term Oxygen Treatment Trial Research Group. N Engl J Med. 2016;375[17]:1617), a recent multicenter randomized study, attempted to answer this question. They studied 738 stable patients with COPD with mild to moderate resting desaturation (Spo₂ 89%-93%) or exercise-induced moderate desaturation (Spo₂ greater than or equal to 80% for greater than or equal to 5 minutes and Spo₂ less than 90% for greater than or equal to 10 seconds during 6- minute walk test). After a median follow-up of 18.4 months, LTOT did not demonstrate a decrease in the time to death or first hospitalization and did not show improvement in quality of life or functional status. Notable adverse events from oxygen included 23 instances of tripping over equipment, with two patients requiring hospitalization and six fires with one patient hospitalized for burns.

A Cochrane meta-analysis, which did not include LOTT data, revealed that oxygen relieved breathlessness during acute exercise in mildly-moderately hypoxemic patients with COPD, but there was insufficient evidence of benefit in daily life or in health-related quality of life (Cochrane Database Syst Rev. 2016;11:CD006429).

Whether or not to continue prescribing oxygen to patients with moderate desaturation remains a controversial issue. A trial of oxygen may be warranted in those who are already on maximal evidence-based therapy for COPD and still complain of severe breathlessness (Ekstrom M; N Engl J Med. 2016;375[17]:1683). Conversely, a patient with COPD and moderate desaturation who resists being placed on supplemental oxygen, can be reassured that this is a reasonable course based on current evidence (Baliksoon R. COPD. 2017;4:71).

Navitha Ramesh, MD, MBBS

Fellow-in-Training Steering Committee Member

Allen Blaivas, DO, FCCP

Steering Committee Member

Informed consent: Do we need to change our practice?

Informed consent is the keystone of clinical research and helps respect and protect the rights of the participants/subjects. While the informed consent process has been standardized, some challenges still remain, such as pieces of information that should be disclosed, how to disclose information and document understanding of participants, and how detailed that disclosure should be (Grady C. N Engl J Med. 2015;372[9]:855). Digital technology can and has been used to improve the process of obtaining informed consent. Smartphones now comprise 75% of all mobile phones sold worldwide. They are being used to reach a larger and diverse population to conduct trials.

Substituting long and complex written forms with electronic consent (e-consent), however, has issues. Few people read through online agreements before clicking “agree,” which may lead to participants consenting without a clear understanding of what they are consenting to. On the other hand, it is also possible to use e-consent to improve comprehension by including videos and graphics. Interactive quizzes can assess the understanding of the participants, and embedded links to audios or videos can further enhance the grasp of information. With e-consents, queries from participants can be answered via phone call or email, etc. When e-consent is obtained remotely, the identity can be confirmed by electronic signatures, username, password, or biometrics.

E-consent has advantages, can be done remotely, no paper is needed, etc. It has potential disadvantages like being costly, videos can add time to the process, and multicenter international trials can be difficult (Grady C, et al. N Engl J Med. 2017;376[20]:e43). Studying e-consents to identify gaps in communication between the researcher and the participant in the digitalized world may help improve the process and allow research to proceed with better understanding of the risks and benefits of involvement in clinical research.

Moshsin Ijaz, MD, FCCP

Steering Committee Member

Early ID and treatment in sepsis

PRISM, the latest meta-analysis of three multicenter trials (ProCESS, ARISE, and ProMISe) found no difference in mortality with early goal-directed therapy vs usual care (N Engl J Med. 2017; 376[23]:2223). These clinical trials promoted early recognition of sepsis and prompt delivery of IV fluids and antimicrobial agents before randomization. It seems that early identification and treatment of sepsis and the rapid administration of antibiotics (following the timing recommended for sepsis bundle protocols) are the most effective interventions in sepsis (Seymour WS, et al. N Engl J Med. 2017;376[23]:2235). Other interventions over the past decade designed to reduce mortality associated with sepsis have been unsuccessful.

However, the recent results of a retrospective before-after clinical study in patients with severe sepsis or septic shock and a procalcitonin greater than 2 ng/mL are encouraging. It suggests that the early use of IV vitamin C, hydrocortisone, and thiamine may reduce mortality and prevent progressive organ dysfunction when compared with matched historical control subjects (Marik PE, et al. Chest. 2017;151[6]:1229). Although vitamin C and thiamine have been reported to be low in critically ill patients, their use in patients with sepsis without deficiency is unclear. In addition, the use of steroids in sepsis has been controversial. A synergistic or overlapping effect of the three agents is a possible explanation. The authors argue that the safety of this combined therapy and potential benefit justifies its implementation pending the confirmation of this single-center study. What is clear is that these encouraging results deserve further study in clinical trials.

Maximiliano Tamae Kakazu, MD, FCCP

Steering Committee Member

The changing landscape of home mechanical ventilation

The greatest advances in home mechanical ventilation for conditions associated with chronic respiratory failure have been associated with the implementation of noninvasivepositive pressure ventilation (NIPPV) via mask interface. This dynamic growth is accredited to NIPPV efficacy and technologic improvements in ventilator and mask. For neuromuscular and restrictive thoracic diseases, NIPPV has been shown to increase survival, decrease hospital admissions, and improve quality of life (Chatwin A, et al. Plos One. 2015;10[5]:e0125839; Annane D, et al. Cochrane Database Syst Rev. 2014;13[12]:CD001941). From this success, NIPPV has been extended to conditions associated with respiratory impairment (eg, COPD, obesity hypoventilation, sleep-disordered breathing). A recent randomized study comparing home oxygen therapy (HOT) plus NIPPV vs HOT alone in post-hospitalized patients with COPD with persistent hypercapnia showed that addition of NIPPV significantly prolonged time to readmission or death from 1.4 to 4.3 months (Murphy P, et al. JAMA. 2017;317[21]:2177). Overall, however, evidence to support NIPPV in these groups is less compelling.

NIPPV is available in both ventilator and respiratory assist device (RAD) models. In addition to delivering basic to complex modes, advantages of a ventilator include portability and option of daytime use with mouth piece ventilation. This creates potential for abuse whereby a supplier could bill for a portable ventilator when an RAD at lower cost would suffice. Monthly rental fee for an RAD ($107-$464) is capped at 13 months, whereas ventilator comes with uncapped rental ($660-$1352) [US Dept HHS, OIG Data Brief 2016, OEI-12-15-00370]. Billing claims for ventilator have shifted from neuromuscular disease to chronic respiratory failure (eg, COPD). Ventilator claims for neuromuscular disease have decreased from 56% in 2009 to 7% in 2015, whereas claims for chronic respiratory failure have increased from 29% in 2009 to 85% in 2015. The substantial increase in claims have no doubt increased burden on health-care systems and resulted in reimbursement cuts.

Current CMS guidelines defer to the provider’s clinical judgment regarding the severity of patient’s respiratory condition and if a ventilator or RAD would be most appropriate. It is important to recognize the proper patient (and setting) who would benefit from advanced respiratory support. The choice of ventilator should be reserved for severe or progressive respiratory impairment, specifically for patients who would benefit from daytime use, and for whom interruption of respiratory support would lead to serious consequences.

Michelle Cao, DO, FCCP

Steering Committee Member

Improving diagnostic capabilities in diffuse parenchymal lung disease

With the approval of two antifibrotic drugs for the treatment of idiopathic pulmonary fibrosis, there has been renewed focus in the NetWork in improving diagnosis in interstitial lung disease. There is considerable interest in exploring novel techniques and paradigms in the classification and diagnosis of diffuse parenchymal lung diseases (DPLDs). Given the invasive nature of surgical lung biopsy and its associated morbidity in elderly patients, there is a need for safer techniques to obtain lung tissue for histopathologic analysis. Transbronchial cryobiopsy may be a safe and accurate alternative for obtaining lung tissue, and we hope to better understand the role of this procedure in disease diagnosis. It is also possible that in the future, we may be able to classify these diseases without having to obtain lung tissue. More studies are being done in novel imaging techniques, such as molecular imaging, optical coherence tomography, and confocal laser endomicroscopy, that may negate the need for lung tissue in the future. Biomarker discovery and identification of biomarker signatures that can help differentiate DPLDs and provide prognostic information are also a particular focus and of importance for our NetWork. With this increased focus on better diagnostic techniques for classification of DPLD, the NetWork is featuring a lecture at CHEST 2017 on “Molecular Endotyping of Pulmonary Fibrosis,” and two sessions that will explore the current diagnostic difficulties that confront clinicians. As we move forward in our understanding of how to classify and diagnose interstitial lung disease, there is potential for more targeted interventions in individual patients.

Tracy Luckhardt, MD

Steering Committee Member

NetWorks: Oxygen therapy, electronic consent, diagnosing ILD