Spirometry is the most common pulmonary function test. It is widely used in the assessment of lung function to provide objective information used in the diagnosis of lung diseases and monitoring lung ...health. In 2005, the American Thoracic Society and the European Respiratory Society jointly adopted technical standards for conducting spirometry. Improvements in instrumentation and computational capabilities, together with new research studies and enhanced quality assurance approaches, have led to the need to update the 2005 technical standards for spirometry to take full advantage of current technical capabilities.
This spirometry technical standards document was developed by an international joint task force, appointed by the American Thoracic Society and the European Respiratory Society, with expertise in conducting and analyzing pulmonary function tests, laboratory quality assurance, and developing international standards. A comprehensive review of published evidence was performed. A patient survey was developed to capture patients' experiences.
Revisions to the 2005 technical standards for spirometry were made, including the addition of factors that were not previously considered. Evidence to support the revisions was cited when applicable. The experience and expertise of task force members were used to develop recommended best practices.
Standards and consensus recommendations are presented for manufacturers, clinicians, operators, and researchers with the aims of increasing the accuracy, precision, and quality of spirometric measurements and improving the patient experience. A comprehensive guide to aid in the implementation of these standards was developed as an online supplement.
Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, ...integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation.
This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed.
Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments.
Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.
In this review, we focus on the potential role of the γ-aminobutyric acidergic (GABAergic) system in age-related episodic memory impairments in humans, with a particular focus on Alzheimer’s disease ...(AD). Well-established animal models have shown that GABA plays a central role in regulating and synchronizing neuronal signaling in the hippocampus, a brain area critical for episodic memory that undergoes early and significant morphologic and functional changes in the course of AD. Neuroimaging research in humans has documented hyperactivity in the hippocampus and losses of resting state functional connectivity in the Default Mode Network, a network that itself prominently includes the hippocampus—presaging episodic memory decline in individuals at-risk for AD. Apolipoprotein ε4, the highest genetic risk factor for AD, is associated with GABAergic dysfunction in animal models, and episodic memory impairments in humans. In combination, these findings suggest that GABA may be the linchpin in a complex system of factors that eventually leads to the principal clinical hallmark of AD: episodic memory loss. Here, we will review the current state of literature supporting this hypothesis. First, we will focus on the molecular and cellular basis of the GABAergic system and its role in memory and cognition. Next, we report the evidence of GABA dysregulations in AD and normal aging, both in animal models and human studies. Finally, we outline a model of GABAergic dysfunction based on the results of functional neuroimaging studies in humans, which have shown hippocampal hyperactivity to episodic memory tasks concurrent with and even preceding AD diagnosis, along with factors that may modulate this association.
•Episodic memory loss is the principal clinical hallmark of Alzheimer’s disease (AD).•Hippocampal hyperactivity correlates with episodic memory failures in aging.•GABA synchronizes neuronal activity in the hippocampus.•GABA levels may be modulated by AD-risk factors.•The GABAergic system may link AD-risk factors and episodic memory decline.
The American Thoracic Society committee on Proficiency Standards for Pulmonary Function Laboratories has recognized the need for a standardized reporting format for pulmonary function tests. Although ...prior documents have offered guidance on the reporting of test data, there is considerable variability in how these results are presented to end users, leading to potential confusion and miscommunication.
A project task force, consisting of the committee as a whole, was approved to develop a new Technical Standard on reporting pulmonary function test results. Three working groups addressed the presentation format, the reference data supporting interpretation of results, and a system for grading quality of test efforts. Each group reviewed relevant literature and wrote drafts that were merged into the final document.
This document presents a reporting format in test-specific units for spirometry, lung volumes, and diffusing capacity that can be assembled into a report appropriate for a laboratory's practice. Recommended reference sources are updated with data for spirometry and diffusing capacity published since prior documents. A grading system is presented to encourage uniformity in the important function of test quality assessment.
The committee believes that wide adoption of these formats and their underlying principles by equipment manufacturers and pulmonary function laboratories can improve the interpretation, communication, and understanding of test results.
In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective ...was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to controls. IL-1α/β induced fibroblast pro-inflammatory responses (CXCL8/IL-8, IL-6, TSLP, GM-CSF) and suppressed ECM-production (collagen, fibronectin, periostin) and the cell's ability to repair and remodel fibrillar collagen I via LOX, LOXL1 and LOXL2 activity, as confirmed by inhibition with β-aminopropionitrile. These data support a role for epithelial-derived-IL-1 in the dysregulated repair of the asthmatic-EMTU and provides new insights into the contribution of airway fibroblasts in inflammation and airway remodeling in asthma.
Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. ...Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.
Exercise-induced bronchoconstriction (EIB) describes acute airway narrowing that occurs as a result of exercise. EIB occurs in a substantial proportion of patients with asthma, but may also occur in ...individuals without known asthma.
To provide clinicians with practical guidance, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB and to develop evidence-based guidelines for the diagnosis and treatment of EIB. The evidence was appraised and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.
Recommendations for the treatment of EIB were developed. The quality of evidence supporting the recommendations was variable, ranging from low to high. A strong recommendation was made for using a short-acting β(2)-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting β(2)-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise.
The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.
In 10 experiments, we investigated the relations among curiosity and people's confidence in their answers to general information questions after receiving different kinds of feedback: yes/no ...feedback, true or false informational feedback under uncertainty, or no feedback. The results showed that when people had given a correct answer, yes/no feedback resulted in a near complete loss of curiosity. Upon learning they had made an error via yes/no feedback, curiosity increased, especially for high-confidence errors. When people were given true feedback under uncertainty (they were given the correct answer but were not told that it was correct), curiosity increased for high-confidence errors but was unchanged for correct responses. In contrast, when people were given false feedback under uncertainty, curiosity increased for high-confidence correct responses but was unchanged for errors. These results, taken as a whole, are consistent with the region of proximal learning model which proposes that while curiosity is minimal when people are completely certain that they know the answer, it is maximal when people believe that they almost know. Manipulations that drew participants toward this region of "almost knowing" resulted in increased curiosity. A serendipitous result was the finding (replicated four times in this study) that when no feedback was given, people were more curious about high-confidence errors than they were about equally high-confidence correct answers. It was as if they had some knowledge, tapped selectively by their feelings of curiosity, that there was something special (and possibly amiss) about high-confidence errors.
Evidence suggests that older adults have difficulty relative to younger adults in forgetting irrelevant information. Here we sought to understand the physical basis of this deficit by investigating ...the relationship between cortical thickness and intentional forgetting, using an item-method directed forgetting task. We tested younger (n = 44) and older (n = 54) adults’ memories for words that they were instructed to either remember or to forget, and then extracted cortical thickness values from brain regions previously shown, using functional neuroimaging, to be associated with memory suppression, including the right inferior frontal gyrus, the right postcentral gyrus and the left superior/middle frontal gyrus. Results from a parallel mediation model indicated that variations in cortical thickness in the right inferior frontal gyrus, but not the right postcentral gyrus or left superior/middle frontal gyrus, partially explained age-related differences in directed forgetting: older adults with thinner cortices in this area showed worse forgetting ability. This is the first study to explore how neuromorphological differences affect the ability to intentionally suppress items in memory. The results suggest that age-related differences in directed forgetting may be partly driven by cortical thickness in a brain structure known to be functionally involved in directed forgetting, and inhibitory control more broadly, supporting a contribution of deficient inhibition to this phenomenon.
The fractional exhaled nitric oxide (FE
) test is a point-of-care test that is used in the assessment of asthma.
To provide evidence-based clinical guidance on whether FE
testing is indicated to ...optimize asthma treatment in patients with asthma in whom treatment is being considered.
An international, multidisciplinary panel of experts was convened to form a consensus document regarding a single question relevant to the use of FE
. The question was selected from three potential questions based on the greatest perceived impact on clinical practice and the unmet need for evidence-based answers related to this question. The panel performed systematic reviews of published randomized controlled trials between 2004 and 2019 and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) evidence-to-decision framework to develop recommendations. All panel members evaluated and approved the recommendations.
After considering the overall low quality of the evidence, the panel made a conditional recommendation for FE
-based care. In patients with asthma in whom treatment is being considered, we suggest that FE
is beneficial and should be used in addition to usual care. This judgment is based on a balance of effects that probably favors the intervention; the moderate costs and availability of resources, which probably favors the intervention; and the perceived acceptability and feasibility of the intervention in daily practice.
Clinicians should consider this recommendation to measure FE
in patients with asthma in whom treatment is being considered based on current best available evidence.
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