Noninvasive ventilation may be beneficial for patients with acute hypercapnic respiratory failure during COPD exacerbations, data indicate

By Dr Deepu

A review of a recent meta-analysis published in the Annals of Emergency Medicine indicates that noninvasive ventilation provides benefit in patients with acute hypercapnic respiratory failure during chronic obstructive pulmonary disease (COPD) exacerbations, reducing mortality and the need for mechanical ventilation.

Authors also added that noninvasive ventilation also may improve length of hospital stay, serum pH, and oxygen partial pressure. The meta-analysis included 17 randomized controlled trials with 1264 patients.

The review authors noted that severe COPD is characterized by hyperinflation, airway obstruction, and decreased respiratory muscle function. In this setting, exacerbation can result in hypercarbic respiratory failure. Usual care includes controlled oxygenation, bronchodilators, corticosteroids, and antibiotics. If these interventions fail, intubation is initiated.

Limitations of the meta-analysis include the variability of usual care and noninvasive ventilation duration in the studies, the potential for publication bias regarding the need for intubation, and low heterogeneity for both mortality and the need for intubation.

The meta-analysis provides strong evidence that noninvasive ventilation reduces mortality, the need for intubation, and hospital length of stay in patients with acute hypercapnic respiratory failure during an acute exacerbation of COPD. The findings support a trial of noninvasive ventilation in patients with a pH of less than 7.30 before proceeding with intubation.

Sputum eosinophil count may predict severity of COPD in smokers, research suggests

- Blood eosinophil count alone not predictive in SPIROMICS cohort
By Dr Deepu

Investigators found that “sputum eosinophil count proved to be a better biomarker of chronic obstructive pulmonary disease (COPD) severity and exacerbations than blood eosinophil count alone in a study involving a large group of smokers with a broad range of airflow obstruction severities.” The investigators found, “in the analysis...blood eosinophil count as a single biomarker was not predictive of sputum eosinophils and was not associated with disease severity or exacerbations unless combined with sputum count.” But, “increased sputum eosinophil inflammation...was found to be associated with more severe COPD, decreased lung function, worse emphysema and air trapping, and a greater likelihood of exacerbations.” The findings were published in The Lancet Respiratory Medicine

Patients enrolled in SPIROMICS had a smoking history of at least 20 pack-years and were recruited from six clinical sites and subsites in the U.S. between November 2010 and spring 2015. All had complete baseline blood cell counts, and a subset had acceptable sputum counts.

A total of 2,499 participants with available blood counts were stratified by mean blood eosinophil count: 1,262 patients with low (<200 cells per μL) and 1,237 with high (≥200 cells per μL) blood eosinophil counts.

A total of 827 patients were eligible for stratification by mean sputum eosinophil percentage including 656 with low (<1.25%) and 171 with high (≥1.25%) sputum eosinophil percentages. Analyses were also conducted involving blood eosinophil cutoffs of 300 cells/μL and sputum eosinophil cutoffs of 2%.

The high sputum eosinophil group had significantly lower median forced expiratory volume in 1 second (FEV)₁ percentage predicted than the low sputum eosinophil group, both before (65.7% [IQR 51.8-81.3] versus 75.7% [59.3-90.2], P<0·0001) and after (77.3% [63.1-88·5] versus 82.9% [67.8-95.9], P=0.001) bronchodilation.

Qualitative computed tomography (CT) density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than in the low sputum eosinophil group and exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (P=0.002).
The main findings of the study are:

FEV₁ percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups

The high blood eosinophil group had slightly increased airway wall thickness (0.02 mm difference, P=0·032), higher St George Respiratory Questionnaire symptom scores (P=0.037), and increased wheezing (P=0.018, but no evidence of an association with COPD exacerbations (P=0.35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, BMI, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage

Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0.64, P<0.0001), but with a high false-discovery rate of 72%

With the higher blood eosinophil cutoff of 300 cells/μL, no significant differences were seen between the high and low count groups. But at the higher 2% sputum eosinophil cutoff, significant differences were seen between the low and high groups for all categories of COPD exacerbations.

The ECLIPSE study reported that 1,483 patients stratified by blood eosinophil counts did not have different numbers of COPD exacerbations in the previous year. Researchers noted that higher blood eosinophils are not associated with COPD exacerbations except when combined with increased sputum eosinophils or with other characteristics, such as a previous history of exacerbations. In the SPIROMICS cohort, higher sputum eosinophil counts alone are associated with exacerbations even in mild to moderate COPD

Survival Rates Have Improved Among Patients With Early Stage NSCLC, Research Indicates

By Dr Deepu

Finally a ray of hope for lung cancer patients, in a finding, researchers report that survival rates have improved among those with early stage disease.

The study included more than 65,000 people diagnosed with stage 1 non-small-cell lung cancer between 2000 and 2010. In that group, 62 percent had surgery, 15 percent received radiation therapy, 3 percent had both surgery and radiation and 18 percent received neither treatment.

The two-year survival rate for people treated with either surgery or radiation therapy rose from 61 percent in 2000 to 70 percent in 2009 -- corresponding to a 3.5 percent annual decrease in death from lung cancer.

Author also noted that while the proportion of patients who did not receive treatment fell from about 20 percent in 2000 to just under 16 percent in 2010, too many still do not receive treatment for "an otherwise highly curable disease."

Read the full study

E-Cigarettes May Cause Unique Harm To Innate Lung Immunity, Research Suggests

By Dr Deepu

Research indicates “e-cigarettes cause unique harm to innate lung immunity, challenging the concept that they are a healthier alternative to traditional cigarettes.” The findings were published in the American Journal of Respiratory Critical Care Medicine.

Researchers collected induced sputum samples from 15 current e-cigarette users, 14 current cigarette smokers, and 15 never-smokers. They analyzed the samples using quantitative proteomics, as well as total and individual mucin concentrations. Neutrophil extracellular trap (NET) formation was also analyzed and compared among the groups.

The researchers found that both cigarette smokers and e-cigarette users had a significant increase in oxidative stress-related proteins, such as thioredoxin (TXN), compared with nonsmokers (P ≤ 0.05 for all levels). These proteins are markers of activation of the innate defense mechanisms associated with lung disease, the researchers explain.

Compared with cigarette smokers and nonsmokers, e-cigarette users had higher levels of neutrophil granulocyte- and NET-related proteins, including matrix metalloproteinase-9 (MMP-9), a major contributor to chronic lung disease (P ≤ 0.05 for all levels). These elevations were seen despite no increase in the sputum neutrophil cell counts.

Total mucin concentrations were highest in the sputum of smokers and were similar among e-cigarette users and nonsmokers. But, mucin composition, which has been correlated to progression of lung disease in previous studies, was similar between smokers and e-cigarette users.

The elevated levels of markers known to be associated with cigarette smoke and lung disease/inflammation, such as TXN and MMP-9, in the sputum of both cigarette smokers and e-cigarette users, indicates commonality in the impacts of these products on airway physiology, such as increased oxidative stress and activation of innate defense mechanisms.
12 of the 15 e-cigarette users smoked cigarettes in the past, and 5 said they occasionally still smoked cigarettes.

Authors wrote "In conclusion, our results challenge the concept that e-cigarettes are a healthier alternative to cigarettes and reverse smoking-induced adverse health effects,".

Emergency funding needed to combat climate change -WMA

By Dr Deepu

 (WMA News Release, October 20, 2017).

A call for national governments to provide designated funds for the strengthening of health systems to combat climate change has come from the World Medical Association. In a policy statement adopted at its annual Assembly in Chicago, the WMA emphasises the urgency for taking action and for emergency planning on local, national and international levels.

WMA President Dr Yoshitake Yokokura said: ‘With the next United Nations conference on climate change less than a month away, it is important that the voice of the world’s physicians is heard about the risks posed to health by climate change’. 

The WMA says that human influence on the climate system is clear, with recent emissions of green-house gases the highest in history. Recent climate changes have had widespread impact on human and natural systems. Compelling evidence proves numerous health risks which threaten all countries. These include more frequent and potentially more severe heatwaves, droughts, floods, storms and bushfires. 

Climate change, especially warming, is already leading to changes in the environment in which disease paths flourish. There is reduced availability and quality of potable water, and worsening food insecurity leading to malnutrition and population displacement. And although climate change is universal, its effects are uneven, with many of the areas most affected the least able to manage the challenges it poses. Those with generally the poorest health and lowest life and health expectancy will be least able to adapt to the adverse effects of climate. 

Dr Yokokura said: ‘We are also urging national governments to provide for the health and wellbeing of people displaced by environmental causes, including those becoming refugees because of the consequences of climate change’

BOOP

By Dr Deepu sourced from Chest Council of India
BOOP

Terminology

Organising pneumonia (OP) is a histologic pattern of alveolar inflammation with varied aetiology (including pulmonary infection). The idiopathic form of OP is called cryptogenic organising pneumonia (COP) and it belongs toidiopathic interstitial pneumonias (IIP's).

COP was previously termed bronchiolitis obliterans organising pneumonia (BOOP), not to be confused with bronchiolitis obliterans per se.
Epidemiology

The presentation is commonest in the 55-60 age group.
Clinical presentation

Patients present with a short history (i.e. less than ~2 months) of breathlessness, non-productive cough, weight loss, malaise and fever. There is no association with smoking.
Pathology

In addition to the alveolar inflammatory changes found with regular pneumonia, there is also the involvement of the bronchioles.

Histologically, it is characterised by mild chronic patchy interstitial inflammation without fibrosis and the presence of buds of granulation tissue made of mononuclear cells, foamy macrophages, and fibrous tissue (Masson bodies) in the distal airspaces which may cause secondary bronchiolar occlusion due to extension of the inflammatory process. Hence, the reason for being previously termed bronchiolitis obliterans organising pneumonia (BOOP).
Radiographic features

Plain radiograph
consolidation unilateral or bilateral patchy areas (commonest finding ): often migratory can affect all lung zones usually peripheral, subpleural, peribronchovascular nodules foci of granulation tissue up to 1 cmmay mimic neoplasm if >5 cm in sizemay be numerous in immunocompromised patients

CT

The most common HRCT features include:

patchy consolidation with a predominantly subpleural and/or peribronchial distribution small, ill-defined peribronchial or peribronchiolar nodules large nodules or masses bronchial wall thickening or dilatation in the abnormal lung regions perilobular pattern with ill-defined linear opacities that are thicker than the thickened interlobular septa and have an arcade or polygonal appearanceground glass opacity or crazy paving

The reverse halo sign (atoll sign) is considered to be highly specific, although only seen in ~20% of patients with COP
History and etymology

It was first described by Davison and colleagues in 1983.
Differential diagnosis

On radiograph consider:

differential for peripheral consolidation:
reverse bat wing opacitiesdifferential for bilateral airspace opacities

On CT consider:

adenocarcinoma in situ or minimally invasive (formerly bronchoalveolar carcinoma)pulmonary lymphoma
pulmonary vasculitis/vasculitides
sarcoidosis chronic eosinophilic pneumonia (for a subpleural consolidative pattern)

Patients With COPD Who Live Alone May Be Less Active, Research Suggests

By Dr Deepu

A recent research suggests “patients with chronic obstructive pulmonary disease (COPD) who live with a spouse, partner, or other caregiver are more active than patients who live alone, and are also more likely to participate in pulmonary rehabilitation programs.” The findings are to be published online in Annals of the American Thoracic Society.
Patients with partners are associated with an 11-fold higher likelihood of participation in a pulmonary rehabilitation program, according to the retrospective analysis of data from the CASCADE (COPD Activity: Serotonin Transporter, Cytokines and Depression) study of depression and functioning among COPD patients, to be published online in Annals of the American Thoracic Society.
The analysis included 282 CASCADE study participants with moderate to severe (GOLD Stage II-IV) COPD (age: 68 ± 9; FEV₁% predicted: 45 ± 16) recruited from two Veterans Administration hospitals and two academic medical centers. Eighty percent of the patients were white men, 90% reported having a family caregiver, and 75% lived with others (family members or friends).

Physical activity was measured with a validated accelerometer at baseline, and at 1 and 2 years. Additional self-care behaviors assessed included pulmonary rehabilitation attendance, smoking status, receipt of influenza and/or pneumococcal vaccinations, and medication adherence.

Structural social support indicators included living status, being partnered, the number of close friends/relatives, and the presence of a family caregiver.

Functional social support was measured with the Medical Outcomes Social Support Survey (MOSSS), and mixed-effects and logistic regression models were also used.

Among the main findings:

Participants who lived with others took 903 more steps per day than those who lived alone (95% CI, 373-1433; P=0.001)
Increases in the MOSSS total score were associated with more steps per day (β=10, 95% CI, 2-18; P=0.02)
The odds of pulmonary rehabilitation participation were more than 11 times higher if a patient had a spouse or partner caregiver compared with not having a caregiver (OR=11.03, 95% CI, 1.93-62.97; P<0.01)
Higher functional social support (MOSSS total score) was associated with marginally lower odds of smoking (OR=0.99, 95% CI, 0.98-1.00; P=0.03) and higher odds of pneumococcal vaccination (OR=1.02, 95% CI,m 1.00-1.03; P=0.02)
No significant relationships were seen between social support and influenza vaccination or adherence with inhaler or nebulizer medications.

FDA approves biosimilar version of bevacizumab

By Dr Deepu

FDA  has approved a “biosimilar version of” Avastin (bevacizumab). “Like the reference product, the biosimilar bevacizumab is approved for use in several types of cancer, including metastatic colorectal cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, cervical cancer, and glioblastoma.” “Like Avastin, the labeling for” the new product, has a boxed warning about an increased risk of: holes in the stomach and intestines; surgery and wound healing complications; and severe or fatal pulmonary, gastrointestinal, central nervous system and vaginal bleeding.”

Behavioral Interventions Help Prevent Anxiety Disorders (JAMA Psychiatry)

By Dr Deepu

Meta-analysis finds small, but significant benefit to these programs
Psychological and/or educational interventions showed a modest benefit for preventing anxiety disorders, a systematic review and meta-analysis found.Researchers  published the data  JAMA Psychiatry. The researchers examined 29 randomized controlled trials comprising over 10,000 patients from 11 countries, and found a small, but significant benefit from psychological and/or educational interventions on anxiety prevention compared to usual care. Most trials examined the benefit of cognitive behavioral therapy, either individualized or through a computerized self-help format. Other examined interventions included psycho-educational, acceptance and commitment therapy and psychosocial interventions.
The significance of the study is this being the first meta-analysis to examine the effectiveness of these methods in anxiety prevention, the authors quoted, and suggested that implementing prevention programs that target a large population could have significant benefit.
I feel this could have a significant contribution in management of stress and anxiety in COPD, which is an ignored entity as of now. Treating these problems will have a positive impact on patients life and he can cope up with his problems with ease.

Poor Sleep May Be Associated With An Increased Risk For Alzheimer’s, Small Study Suggests

By Dr Deepu

“Poor sleep may be an indication of increased risk for Alzheimer’s disease,” researchers found after studying “101 cognitively normal people, average age 63.” All participants had their “spinal fluid for the presence of indicators of the plaques and tangles that are characteristic of Alzheimer’s.” After controlling for confounding factors, the study authors found that “poor sleep quality, sleep problems and daytime sleepiness were associated with increased spinal fluid indicators of Alzheimer’s disease.”
The highlights of the study
They Investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention.
101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal.
Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein–1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin).
Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.

Results: Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
No significant associations between sleep and NFL or neurogranin.

Conclusions: Self-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.

The findings were published online July 5 in Neurology. 

Sleep Apnea May Increase Risk Of Patients With Type 2 Diabetes Developing Advanced Retinopathy, Study Suggests

By Dr Deepu

A study has revealed that patients with sleep apnea who also have type 2 diabetes “have more than double the risk of worsening retina disease compared to diabetics without the sleep breathing disorder,”. The study was published in the American Journal of Respiratory and Critical Care Medicine. Researchers found that 43% of the study participants who had type 2 diabetes and sleep apnea had diabetic retinopathy, compared to 24% of participants who had type 2 diabetes without sleep apnea.

Are WHO approved nucleic acid amplification tests causing large-scale "false identification" of rifampicin-resistant tuberculosis?

By Dr Deepu

The nucleic acid amplification tests (NAATs): Line probe assay and GeneXpert (Xpert) have evolved as the primary tool for identification of rifampicin (RIF)-resistant (RR) tuberculosis (TB) worldwide, primarily because of the ease and speed. They rechecked RR isolates identified by NAATs from presumptive RR TB cases belonging to South India by the Revised National TB Control Program, India using multiple RIF concentrations on Bactec MGIT system and compared the mutation patterns with the resistance levels.
Researchers state that they used standard protocol for Bactec MGIT system as given by the manufacturer modified for the multiple RIF concentrations. All the retests were done in a certified BSL3 laboratory.
Astonishingly they found that there is a mismatch of up to 20% (RIF breakpoint 0.5 mg/L); the NAATs probably overidentifying RR TB. Half of the cases with mismatch showed a sub-breakpoint rise in resistance level (0.125 mg/L to 0.5 mg/L RIF).
They finally concluded by stating probable reasons for the mismatch are "sub-breakpoint low-level resistance mutants," hetero-resistant bacterial populations, and other inherent test limitations along with the low RR TB prevalence in South India (<5%) among "presumptive multidrug-resistants." They also quoted, could be due to the incomplete selection pressure by an inadequate RIF exposure caused by various factors including a low-RIF dosage being used widely and poor Directly observed treatment.
They concluded"To prevent the false diagnosis of RR TB in a massive scale when using NAATs, we may need to enforce a carefully targeted testing approach and a phenotypic susceptibility testing with multiple RIF concentrations for confirmatory purposes".
Find the full text article here

Diaphragm Palsy

By Dr Deepu, image and video Courtesy Dr Rajesh
A 61 yr old male, never smoker, no lung issues, developed GBS  (guillian barre).   Post IvIG therapy he was recovering well.   Then the consulting neurologist noticed that he is in respiratory distress. Below is his cxr and video showing his breathing pattern.

Diaphragmatic paralysis can be unilateral or bilateral.

Clinical presentation

Clinical features are highly variable according to underlying aetiological factor

unilateral paralysis: asymptomatic in most of the patients as the other lung compensates.may have dyspnea, headaches, fatigue, insomnia and overall breathing difficultybilateral diaphragmatic palsy can be a medical emergency; they present with severe dyspnea, even with mild exertion


Radiographic featuresPlain radiograph

Normally the right dome of the diaphragm is higher in position as compared to the left dome, if the left dome of the diaphragm is elevated (>2 cm) diaphragmatic palsy should be suspected.

Fluoroscopy

Fluoroscopic examination of the diaphragm ("sniff test") very useful in diagnosing a diaphragmatic paralysis. In normal individuals, both hemidiaphragm will descend with inspiration. In cases of unilateral diaphragmatic paralysis, the affected side demonstrates a paradoxical upward movement.

Ultrasonography

An alternative to fluoroscopy in diagnosing this condition, particularly useful in the paediatric population. Real-time ultrasound is ideal for evaluation of spontaneous respiratory diaphragmatic motion (may require temporary disconnection of the ventilator). This can be performed in the axial plane to compare the two hemidiaphragm simultaneously. Additional coronal or sagittal M-mode can help quantify the degree of movement of each individual hemidiaphragm. Diagnostic criteria include paradoxical movement, excursion of less than 4 mm, and a difference > 50% between the excursion of one hemidiaphragm compared to the other.

Treatment and prognosis

Patients with unilateral diaphragmatic paralysis do not require treatment. There may be an option for phrenic nerve stimulation in some cases.