Phase-Resolved Functional Lung (PREFUL) MRI to Quantify Ventilation: Feasibility and Physiological Relevance in Severe Asthma.

Rationale And Objectives: Emergent evidence in several respiratory diseases supports translational potential for Phase-Resolved Functional Lung (PREFUL) MRI to spatially quantify ventilation but its feasibility and physiological relevance have not been demonstrated in patients with asthma. This study compares PREFUL-derived ventilation defect percent (VDP) in severe asthma patients to healthy controls and measures its responsiveness to bronchodilator therapy and relation to established measures of airways disease.

Materials And Methods: Forty-one adults with severe asthma and seven healthy controls performed same-day free-breathing H MRI, Xe MRI, spirometry, and oscillometry.

Specific Ventilation in Severe Asthma Evaluated with Noncontrast Tidal Breathing H MRI.

Purpose To determine if proton (H) MRI-derived specific ventilation is responsive to bronchodilator (BD) therapy and associated with clinical biomarkers of type 2 airway inflammation and airways dysfunction in severe asthma. Materials and Methods In this prospective study, 27 participants with severe asthma (mean age, 52 years ± 9 [SD]; 17 female, 10 male) and seven healthy controls (mean age, 47 years ± 16; five female, two male), recruited between 2018 and 2021, underwent same-day spirometry, respiratory oscillometry, and tidal breathing H MRI. Participants with severe asthma underwent all assessments before and after BD therapy, and type 2 airway inflammatory biomarkers were determined (blood eosinophil count, sputum eosinophil percentage, sputum eosinophil-free granules, and fraction of exhaled nitric oxide) to generate a cumulative type 2 biomarker score.

Circulating anti-nuclear autoantibodies in COVID-19 survivors predict long COVID symptoms.

Background: Autoimmunity has been reported in patients with severe coronavirus disease 2019 (COVID-19). We investigated whether anti-nuclear/extractable-nuclear antibodies (ANAs/ENAs) were present up to a year after infection, and if they were associated with the development of clinically relevant post-acute sequalae of COVID-19 (PASC) symptoms.

Methods: A rapid-assessment line immunoassay was used to measure circulating levels of ANAs/ENAs in 106 convalescent COVID-19 patients with varying acute phase severities at 3, 6 and 12 months post-recovery.

Airway autoantibodies are determinants of asthma severity.

Background: Local airway autoimmune responses may contribute to steroid dependence and persistent eosinophilia in severe asthma. Auto-IgG antibodies directed against granule proteins such as eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO) and nuclear/extranuclear antigens (antinuclear antibodies (ANAs)) have been reported. Our objective was to describe the prevalence and clinical characteristics of asthmatic patients with airway autoreactivity, and to assess if this could be predicted from clinical history of autoreactivity.

CFTR heterozygosity in severe asthma with recurrent airway infections: a retrospective review.

Rationale: Patients with asthma who have neutrophilic bronchitis may have an underlying cause leading to increased susceptibility to airway infections.

Methods: Retrospective review of patients with asthma who had a previous history of recurrent exacerbations that had been associated with airway or sinus infections referred to a tertiary asthma center between 2005 and 2020. Demographics, clinical features, and airway inflammation type determined by sputum cytometry were compared between CFTR carriers and non-carriers.

Iron in airway macrophages and infective exacerbations of chronic obstructive pulmonary disease.

Background: Excess pulmonary iron has been implicated in the pathogenesis of lung disease, including asthma and COPD. An association between higher iron content in sputum macrophages and infective exacerbations of COPD has previously been demonstrated.

Objectives: To assess the mechanisms of pulmonary macrophage iron sequestration, test the effect of macrophage iron-loading on cellular immune function, and prospectively determine if sputum hemosiderin index can predict infectious exacerbations of COPD.

Bronchial thermoplasty guided by hyperpolarised gas magnetic resonance imaging in adults with severe asthma: a 1-year pilot randomised trial.

Patient-specific localisation of ventilation defects using hyperpolarised gas magnetic resonance imaging (MRI) introduces the possibility of regionally targeted bronchial thermoplasty (BT) for the treatment of severe asthma. We aimed to demonstrate that BT guided by MRI to ventilation defects reduces the number of radiofrequency activations while resulting in improved asthma quality-of-life and control scores that are non-inferior to standard BT. In a 1-year pilot randomised controlled trial, 14 patients with severe asthma who were clinically eligible to receive BT underwent hyperpolarised gas MRI to characterise ventilation defects and were randomised to MRI-guided or standard BT.

Underestimation of airway luminal eosinophilia by quantitative sputum cytometry.

Rationale: On Wright-stained sputum cytospins, eosinophil differential of ≥ 1.2% is considered abnormal, and ≥ 2.3% identifies an eosinophilic endotype.

Lessons of the month: A breathless severe asthmatic in the genomic era: Occam's razor or Hickam's dictum?

Breathlessness is a subjective symptom that may stem from a number of pathological and functional aetiologies. Consequently, clinicians are often faced with the challenge of navigating between the tensions of Occam's razor (parsimonious aetiology) or Hickam's dictum (multiple diagnoses). We report a case of a 36-year-old woman with a lifelong history of episodic breathlessness caused at various times by dysfunctions of lung parenchyma (emphysema) and airway smooth muscle (asthma), skeletal muscle (filamin-C fibrillary myopathy) and cardiac muscle (cardiomyopathy).

Narrative Physicalization: Supporting Interactive Engagement With Personal Data.

Physical engagement with data necessarily influences the reflective process. However, the role of interactivity and narration are often overlooked when designing and analyzing personal data physicalizations. We introduce Narrative Physicalizations, everyday objects modified to support nuanced self-reflection through embodied engagement with personal data.

Effects of Anti-T2 Biologic Treatment on Lung Ventilation Evaluated by MRI in Adults With Prednisone-Dependent Asthma.

Background: The functional consequence of airway obstruction in asthma can be regionally measured using inhaled gas MRI. Ventilation defects visualized by MRI persist post-bronchodilator in patients with severe asthma with uncontrolled sputum eosinophilia and may be due to eosinophil-driven airway pathology that is responsive to "anti-T2" therapy.

Research Question: Do anti-T2 therapies that clear eosinophils from the airway lumen decrease ventilation defects, measured by inhaled gas MRI, in adults with prednisone-dependent asthma?

Study Design And Methods: Inhaled hyperpolarized gas MRI was performed before and after bronchodilation in 10 prednisone-dependent patients with asthma with uncontrolled eosinophilic bronchitis (sputum eosinophils ≥3%) at baseline and 558 (100-995) days later when their eosinophilic bronchitis had been controlled (sputum eosinophils <3%) by additional anti-T2 therapy.

Omalizumab in patients with severe asthma and persistent sputum eosinophilia.

Omalizumab, a recombinant humanized monoclonal antibody targeting the IgE molecule, is the first biologic approved for moderate-to-severe allergic asthmatics, who remain uncontrolled despite high dose inhaled corticosteroid and bronchodilators. Steroid-sparing effect of omalizumab has not been demonstrated in asthmatics with persistent airway eosinophilia in a randomised controlled trial till date. From this double-blind, placebo-controlled, multi-centred, randomized parallel group design, we report that omalizumab is possibly inadequate to control sputum eosinophilia, and therefore may not have a steroid-sparing effect, especially in those maintained on oral corticosteroids daily.

Sputum Antineutrophil Cytoplasmic Antibodies in Serum Antineutrophil Cytoplasmic Antibody-Negative Eosinophilic Granulomatosis with Polyangiitis.

Rationale: Eosinophilic granulomatosis with polyangiitis (eGPA) is a small-vessel vasculitis where 40% of patients present with serum antineutrophil cytoplasmic antibodies (ANCAs). We examined the presence and clinical relevance of sputum ANCAs in the serum ANCA patients with eGPA.

Methods: ANCA was investigated in matched sputum and blood samples collected from 23 patients with eGPA (n = 10, serum ANCA), 19 patients with eosinophilic asthma (prednisone dependent), and 13 healthy volunteers.

Loss of bronchoprotection to Salbutamol during sputum induction with hypertonic saline: implications for asthma therapy.

Background: Sputum induction with hypertonic saline in obstructive airway diseases is generally safe. However, saline induces bronchoconstriction in some patients despite pre-medication with Salbutamol. Our objectives were to investigate the predictors of failure of Salbutamol to protect against saline-induced-bronchoconstriction in patients with asthma and COPD and to evaluate implications for asthma therapy.