Skylar Jeremias

 (COPD) before the age of 50 is generally associated with tobacco smoking, recent study results indicated that familial and personal history with respiratory events may offer an explanation for why some younger people develop COPD.

Other research has shown that lung function declines swiftly in about half of patients with COPD who are current or former smokers, while the other half have a normal rate of lung function decline stemming from abnormal lung function beginning in early adulthood.

The current study sought to illustrate the characteristics of COPD when it develops prior to the age of 50. The study, 

, analyzed 92 cases of patients with post-bronchodilator forced expiratory volume in 1 second (FEV

) or a forced vital capacity (FVC) of less than 0.7 with matched controls, all of whom were current or former smokers between the ages of 35 and 50. Participants were recruited from 12 hospitals and primary care practices in Spain.

Overall, researchers found 6 independent characteristics associated with early COPD occurrence, including family history with respiratory events, past personal history or hospitalization at a young age due to respiratory events, symptoms, cumulative smoking exposure in pack-years, low diffusing capacity, and unemployment.

Those with COPD reported that their parents had respiratory conditions in a higher proportion than those without COPD, with the most common conditions being maternal and paternal bronchitis and maternal cardiac disease.

Additionally, 12% reported being hospitalized before the age of 5 years for respiratory reasons, compared with 3% from the control group (

Individuals with COPD also had higher proportions of chronic bronchitis than those without (25.84% vs 10.15%, 

= .00112) and were significantly more likely to have a diagnosed respiratory disease, such as asthma, and use medications to treat those conditions.

Only 46% of individuals (36 out of 78) with a previous diagnosis for COPD reported regular use of over-the-counter respiratory medications. Those who had undiagnosed COPD were referred to a health care provider for treatment.

Many in the control group had normal spirometry but still had structural and functional abnormalities seen in patients with COPD, such as mid-expiratory airflow characterized by a forced expiratory flow at 25%-75% of FVC, which was reduced in both groups (39.2±30.9% ref. vs 92.6±35.5% ref., 

There was also evidence of lung damage in both groups: 231 of the participants had CAT scans of the thorax, and emphysema was seen in 61% of patients with COPD and 32% of those without (

“In any case, this observation confirms that smokers with normal spirometry may have emphysema and strengthens the need for a careful reconsideration of the diagnosis and taxonomy of COPD,” noted researchers in the report.

Researchers said that some factors associated with early COPD, such as early-life events and smoking exposure, may actually be risk factors, whereas symptoms, reduced lung diffusion, and unemployment may be considered to be consequences of COPD.

“Collectively, these observations contribute to a better understanding of early COPD and may open novel opportunities for prevention and treatment of the disease,” the authors said in the study.​ 

Also, researchers said that these factors contribute to a better comprehension of phenotypic characteristics of early COPD and could aid in determining which young smokers are more likely to be at risk of developing the disease.

Cosío BG, Pascual-Guardia S, Borras-Santos A, et al. Phenotypic characterisation of early COPD: a prospective case–control study. 

. 2020; 6(4):1-13. doi: 10.1183/23120541.00047-2020.

Articles

A study analyzed the personal and family history of patients who developed chronic obstructive pulmonary disease (COPD) before age 50.

Early-Onset COPD Often Associated With Family History, Study Says

Merck’s pembrolizumab (Keytruda) received an expanded list of indications to include relapsed or refractory classical Hodgkin 

 (cHL) in adults, making it the first anti-PD-1 therapy to be approved for this indication.

Additionally, the FDA granted an undated pediatric indication for

to include refractory cHL and cHL that has relapsed after 2 or more lines of therapy.

“An estimated 8500 patients in the US, many of them 40 years of age or younger, will be diagnosed with cHL this year. Now, patients with cHL who progress after frontline therapy have a new option in Keytruda,” Vicki Goodman, MD, vice president of Clinical Research at Merch Research Laboratories, said 

was approved as a 100 mg injection for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after 3 or more prior lines of therapy as well as several 

other types of cancer, including gastric, esophageal, cervical, melanoma, lung, and renal cancers.

for patients with recurrent or metastatic cutaneous squamous cell carcinoma that is not curable by surgery or radiation.

 original approval was part of the FDA’s Project Orbis, which is conducted by the FDA Oncology Center of Excellence allowed for the submission and review of oncology drugs among the agency’s international partners. The FDA is working alongside the Australian Therapeutic Good Administration and Health Canada on the ongoing review.

“The patients with cHL who do not achieve remission following initial treatment or who relapse after transplantation face a poor prognosis, reflecting the unmet need for improved therapies in the relapsed/refractory setting….With this approval, Keytruda has the potential to change the current standard of care and help these patients achieve better outcomes,” said John Kuruvilla, MD, hematologist and associate professor of medicine at Princess Margaret Cancer Centre and University of Toronto, in a statement.

The approval for the expanded indication is based on positive results from a randomized, open-label, active-controlled trial conducted in 304 patients with relapsed or refractory cHL phase 3 trial. The KEYNOTE-204 trial, comparing 

 with brentuximab vendotin (BV), reduced the disease progression or death risks by 35% (HR = 0.65; 95% CI, 0.48-0.88; 

The trial also revealed that median progression-free survival (PFS) was 13.2 months (95% CI, 10.9-19.4) for patients treated with 

 compared with BV, which had a PFS of 8.3 months (95% CI, 5.7-8.8).

Serious adverse reactions were reported in 30% of patients who took 

 The most commonly reported serious adverse reactions included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia, and sepsis.

Adverse reactions were the cause of discontinuation for 14% of patients; 30% of patients had dosage interruptions due to AEs.

The most frequently reported adverse reactions, affecting greater than or equal to 20% of patients, were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), pyrexia (20%), fatigue (20%), rash (20%), and cough (20%). The most commonly reported adverse reactions that resulted in dosage interruptions were upper respiratory tract infection, pneumonitis, transaminase increase, and pneumonia.

It is the first PD-1 inhibitor to be approved to be used as a monotherapy for the treatment of adult and pediatric patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL).

Pembrolizumab Expanded to Treat Relapsed, Refractory cHL in Adults, Children

Results of a phase 1 study of healthy adults receiving either of Pfizer and BioNTech’s 2 RNA-based vaccine candidates for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) supported the decision about which one to advance to later trials, researchers wrote Wednesday.

, the authors said older adults had fewer systemic effects from BNT162b2 compared with BNT162b1. Pfizer has moved BNT162b2 into late-stage trials.

The study is part of Pfizer and BioNTech’s larger trial to find a vaccine to prevent SARS-CoV-2 from causing coronavirus disease 2019 (COVID-19). Previous studies conducted in Germany and the United States narrowed down the companies’ investigation to these 2 candidates.

Researchers have begun trial enrollment for a phase 2/3 international trial that will assess the safety and efficacy profile of BNT162b2 at the 30-μg dose level in up to 44,000 participants aged 18 to 85 years.

In the phase 1 study to evaluate safety and immunogenicity, a total of 195 healthy participants underwent a 4:1 randomization in 13 groups to either receive a placebo or vaccine candidate. Each group had 15 participants, where 12 would receive a vaccine candidate and 3 would receive a placebo.

Participants were aged 18 to 55 years and 65 to 85 years.

The ongoing, placebo-controlled, observer-blinded, dose-escalated phase 1 trial tested dosages of 10 μg, 20 μg, 30 μg, and 100 μg.

All of the groups received 2 doses administered 21 days apart, except for the group receiving 100 μg of BNT162b1, who only received 1 dose because patients who received the active vaccine experienced reactogenicity.

Severe systemic reactions, including fatigue, headache, chills, muscle pain, and joint pain, were reported in a small number of younger patients who received BNT162b2. However, none of the older recipients of BNT162b2 reported severe reactions.

The study’s results come days after pauses were announced for Johnson & Johnson’s and Eli Lilly’s vaccine trials. AztraZeneca’s vaccine trial was also temporarily halted in late September.

 in response to being mentioned by the president during the first presidential debate, 

that the company will not succumb to political pressure or cut corners on development. 

 penned a letter to Bourla urging him to follow safety standards and wait until all participants in the phase 3 trial have received their second dose of the vaccine and that monitoring should occur through late November before filing for an Emergency Use Authorization.

Walsh, EE, French RW, Falsey AR, et al. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates. 

. Published October 14 2020. doi:10.1056/NEJMoa2027906

Study results from a phase 1 trial looking at 2 RNA-based severe acute respiratory syndrome coronavirus 2 vaccine candidates give further insight into the candidates’ safety profiles.

Study Backs Decision to Move Forward With Pfizer Vaccine Candidate

A young man in Nevada is the first reported case of coronavirus disease 2019 (COVID-19) reinfection in the United States and the fifth case of reinfection worldwide, according to a new case study published Monday. The second reinfection was more serious than the first, but he has since recovered.

Previously, there have been 4 other reinfection cases, including in Hong Kong, Belgium, the Netherlands, and Ecuador.

Besides the United States, Ecuador is the only other country to have a reinfection case that resulted in increased symptom severity during the patient’s second infection. In Hong Kong, Belgium, and the Netherlands, the reinfected patients did not have more severe symptoms.

The reinfection occurred in a 25-year old man who had no known immune disorders. After testing positive in April to SARS-CoV-2, the virus that causes COVID-19, and was mildly ill, he tested negative on 2 subsequent occasions. In June, he was hospitalized and retested as positive after experiencing severe COVID-19 symptoms, including fever, headache, dizziness, cough, nausea, and diarrhea. He also needed oxygen.

Mark Pandori, PhD, lead author of the study and director of the Nevada State Public Health Laboratory and associate professor of Pathology at the School of Medicine at the University of Nevada in Reno, said in a statement that the case study suggests that people who have previously tested positive for COVID-19 should continue to take serious precautions, including practicing social distancing, wearing face masks, and handwashing.

The genomes of the patient’s virus samples from April and June displayed significant genetic differences between them, suggesting that the patient was infected twice by 2 distinct COVID-19 infections.

Researchers suspected that the patient may have contracted the second infection from a parent whom they live with that also tested positive for the virus in June, but genomic sequencing has not yet confirmed this.

, raised the concern that reinfection could affect the efficacy of emerging vaccines as the virus has the potential for genomic variations.

“If we have truly reported a case of reinfection, initial exposure to SARS-CoV-2 might not result in a level of immunity that is 100% protective for all individuals. With respect to vaccination, this understanding is established, with influenza regularly showing the challenges of effective vaccine design,” the researchers wrote.

In a comment on the study, Akiko Iwasaki, PhD, a professor of Immunobiology and Molecular, Cellular and Developmental Biology at Yale University, who was not part of the work, explained that although current research is able to detect differences in viral genome sequences, there is no evidence that a SARS-CoV-2 has emerged as a result of immune evasion, meaning that the current vaccines in development will likely provide protection against all circulating variants of the virus.

“As more cases of reinfection surface, the scientific community will have the opportunity to understand better the correlates of protection and how frequently natural infections with SARS-CoV-2 induce that level of immunity. This information is key to understanding which vaccines are capable of crossing that threshold to confer individual and herd immunity,” wrote Iwasaki.

The study authors offered 3 explanations for the patient’s worsened symptom severity, including that the second infection could have resulted from a higher dose of the virus than the first infection; the second infection was caused by a more virulent version of the virus; or that the previously developed antibodies could make a subsequent infection worse, which researchers have observed with the SARS-CoV betacoronavirus as well as other diseases, such as dengue fever.

Furthermore, the authors explained that there is a small possibility that the second infection resulted from some form of deactivation and reactivation. However, the authors said they doubted this hypothesis because the mutational rate of the virus needed for this to occur has presently not been observed.

Another alternative explanation would be a simultaneous co-infection of both viral strains. But the authors noted that this would mean that the second strain would have gone undetected in April, and conversely, the first strain would have needed to be depleted prior to the patient’s testing in June. This possibility also does not account for the genotype switch in the patient.

“We need more research to understand how long immunity may last for people exposed to SARS-CoV-2 and why some of these second infections, while rare, are presenting as more severe…So far, we’ve only seen a handful of reinfection cases, but that doesn’t mean there aren’t more, especially as many cases of COVID-19 are asymptomatic. Right now, we can only speculate about the cause of reinfection,” said Pandori in a statement.

Pandori also noted that the current lack of comprehensive genomic sequencing of COVID-19 cases, as well as the lack of screening and testing, limits the ability of researchers and public health officials to diagnose, monitor, and obtain genetic tracking for the virus.

Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. 

Published online October 12 2020. doi: 10.1016/S1473-3099(20)30764-7.

The United States has its first reported of coronavirus disease 2019 (COVID-19) reinfection, in a young male patient with no underlying immune conditions.

Author | Skylar Jeremias

Articles

Early-Onset COPD Often Associated With Family History, Study Says

Pembrolizumab Expanded to Treat Relapsed, Refractory cHL in Adults, Children

Study Backs Decision to Move Forward With Pfizer Vaccine Candidate

First Case of COVID-19 Reinfection Detected in the US