Will inhalational GM-CSF replace whole lung lavage as a treatment for autoimmune pulmonary alveolar proteinosis? Many pole positions, not yet the final winner
Extract Autoimmune pulmonary alveolar proteinosis (aPAP) is associated with autoantibodies against granulocyte–macrophage colony-stimulating factor (GM-CSF) in serum, causing the disruption of GM-CSF signal and the functional failure of alveolar macrophages and neutrophils [1]. As a result, surfactant phospholipids and proteins accumulate in the alveoli, leading to respiratory insufficiency [1]. In addition, aPAP patients are prone to opportunistic respiratory infections, mainly related to neutrophil dysfunction [2]. Whole lung lavage (WLL), which mechanically removes accumulated surfactant from alveoli, is still con...
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Bonella, F., Manali, E. D., Papiris, S. A. Tags: Editorials Source Type: research

CXCL6 in idiopathic pulmonary fibrosis: a novel mediator in the complex epithelial-mesenchymal crosstalk
Extract Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive disease of pulmonary fibrosis [1, 2]. In the 20th century, IPF was considered a chronic inflammatory disease characterised by the accumulation of inflammatory cells in the alveoli in response to key chemokines, triggering persistent damage to lung tissue and consequent pathological scarring [3]. This pathophysiological model was the driver of therapeutic approaches, relying on corticosteroids, immunosuppressants and antioxidants [4]. However, intense mechanistic studies since the early 21st century and, eventually, the failure of the PANTHER trial [5...
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Helou, D. G., Crestani, B. Tags: Editorials Source Type: research

Cognitive behavioural therapy sessions approach ineffective for anxiety and depression in COPD: is the door closed for good?
Extract We read with great interest the original work by Taylor et al. [1]. This multicentre, pragmatic, randomised controlled trial (RCT) examined the efficacy of a brief intervention incorporating education and cognitive behavioural therapy (CBT) principles to treat mild to moderate anxiety and depression symptoms in patients with COPD. We applaud the authors for their meticulous work in designing and executing this RCT, the largest of its kind evaluating the impact of a novel intervention of tailored psychological interventions for anxiety or depression in COPD (the TANDEM study). TANDEM was a home-based intervention wi...
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Yohannes, A. M., Iyer, A. S., Hoth, K. F., Dransfield, M. T. Tags: Correspondence Source Type: research

Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients
Conclusions This long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Campo, I., Carey, B. C., Paracchini, E., Kadija, Z., De Silvestri, A., Rodi, G., De Amici, M., Torre, C., Zorzetto, M., Griese, M., Meloni, F., Corsico, A. G., Trapnell, B. C., Mariani, F. Tags: Interstitial and orphan lung disease Original Articles: Orphan disease Source Type: research

The skeletal muscle metaboreflex: a novel driver of ventilation, dyspnoea and pulmonary haemodynamics during exercise in pulmonary arterial hypertension
Extract Impairment of exercise capacity, predominantly limited symptomatically by dyspnoea [1], affects most patients with pulmonary arterial hypertension (PAH) despite current therapies [2], with significant implication for patients, adversely impairing health-related quality of life [3] and clinical prognosis [4]. However, the underpinning physiological mechanisms behind dyspnoea and exercise limitation remain incompletely understood. Skeletal muscle metabolic and microcirculatory deficits are present in PAH [2], and likely lead to earlier and more pronounced accumulation of metabolites during exercise. We hypothesised t...
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Plunkett, M. J., Sayegh, A. L. C., McWilliams, T. J., Sithamparanathan, S., Paton, J. F. R., Fisher, J. P. Tags: Pulmonary vascular disease Research Letters Source Type: research

Genome-wide association study of preserved ratio impaired spirometry (PRISm)
Conclusion This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Higbee, D. H., Lirio, A., Hamilton, F., Granell, R., Wyss, A. B., London, S. J., Bartz, T. M., Gharib, S. A., Cho, M. H., Wan, E., Silverman, E., Crapo, J. D., Lominchar, J. V. T., Hansen, T., Grarup, N., Dantoft, T., Karhus, L., Linneberg, A., O'Connor, Tags: Genetics Original Articles: Genetic epidemiology Source Type: research

Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis
Conclusions CXCL6 is expressed in ectopic airway epithelial cells. Elevated levels of CXCL6 are associated with IPF mortality. CXCL6-driven collagen synthesis represents a functional consequence of ectopic localisation of airway epithelial cells in IPF. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 4, 2024 Category: Respiratory Medicine Authors: Bahudhanapati, H., Tan, J., Apel, R. M., Seeliger, B., Schupp, J., Li, X., Sullivan, D. I., Sembrat, J., Rojas, M., Tabib, T., Valenzi, E., Lafyatis, R., Mitash, N., Hernandez Pineda, R., Jawale, C., Peroumal, D., Biswas, P., Tedrow, J., Adams, T., Kamins Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

Peripheral pulmonary artery stenosis in adults: a novel type of pulmonary vascular disease with a strong genetic background
Extract Group 4 pulmonary hypertension (PH) includes several conditions associated with obstructions in the pulmonary arterial tree. Chronic thromboembolic PH (CTEPH), the most common type of group 4 PH in adults, has attracted the most attention to date. In this condition, the rise in pulmonary artery pressure results from a combination of the obstruction to flow caused by organised thrombus and pulmonary arterial hypertension (PAH)-like microvascular disease, which develops as a result of excessive blood flow and shear stress in unobstructed areas of the lung. For this reason, CTEPH is typically managed both through mech...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Constantine, A., Dimopoulos, K., Gerges, C., Lang, I. M. Tags: Editorials Source Type: research

Having new eyes: MRI for visualisation of pulmonary vascular disease and prediction of bronchopulmonary dysplasia severity
Extract Marcel Proust wrote that "the real voyage of discovery... consists not in seeking new landscapes but in having new eyes [1]." Indeed, our ability to noninvasively visualise the structure and function of human tissues has rapidly evolved. 130 years after Nikola Tesla described the first rotational magnetic field, modern magnetic resonance imaging (MRI) has transformed the ability to "see" the inner structures of human organs without having to surgically dissect them [2]. Innovative MRI protocols now allow for functional cardiac assessment and quantification of flow through the pulmonary circulation [3]. The study re...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Sucre, J. M. S., Frank, D. B. Tags: Editorials Source Type: research

Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: sorting the chicken and the egg by genetic link
Extract Idiopathic pulmonary fibrosis (IPF) is a devastating condition that confers substantial morbidity and significantly reduces lifespan. Because of this, investigators have searched for modifiable risk factors to reduce the burden of IPF. While the aetiological holy grail for IPF remains elusive, there is mounting evidence that prevalent lung injuries on a background of genetic susceptibility culminate in this rare and "idiopathic" disease. Gastro-oesophageal reflux may be one of these prevalent lung injuries that culminate in lung fibrosis. In preclinical models, gastric acid aspiration into the lungs can trigger an ...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Newton, C. A., Noth, I., Raghu, G. Tags: Editorials Source Type: research

AMR-Lung: a European Clinical Research Collaboration on antimicrobial resistance in chronic lung disease
Extract Antimicrobial therapies, such as antibiotics and antifungals, occupy an important place in the treatment of patients with chronic respiratory diseases, such as bronchiectasis (including related to underlying cystic fibrosis (CF) and primary ciliary dyskinesia (PCD)) and COPD. These patients often become colonised with respiratory pathogens, which may cause chronic infection and play a role in acute exacerbations, episodes of increased airway inflammation with respiratory symptoms, that are usually infectious in origin. Depending on the underlying disease and patient conditions, antibiotics are commonly used to erad...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Thee, S., Ekkelenkamp, M., Shah, A. Tags: Editorials Source Type: research

Epigenome-wide association studies: the exposures of yesterday form the methylations of tomorrow
Extract Technological advances spur scientific discovery. This is certainly true for epigenomics, particularly DNA methylation (DNAm) analysis. Illumina's Infinium bead array platform has drastically evolved since the first array in 2010, now capturing >850 000 DNAm sites and has been used in over 8500 publicly available human datasets (gene expression omnibus; www.ncbi.nlm.nih.gov/geo/) spanning multiple organs, tissues and cell types. DNAm describes when a methyl group is chemically bound to a cytosine residue in DNA. The presence of this group can sterically interfere with gene expression through various complex mech...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Weckmann, M., Reddy, K. D. Tags: Editorials Source Type: research

The results of genetic analysis and clinical outcomes after stent deployment in adult patients with isolated peripheral pulmonary artery stenosis
Extract Peripheral pulmonary arterial stenosis (PPAS) is commonly observed in paediatric patients with associated congenital heart disease or systemic congenital syndromes, such as tetralogy of Fallot and Williams syndrome [1]. Meanwhile, isolated PPAS without other structural heart disease or systemic congenital syndromes is primarily reported in adulthood [2]. Recent genetic analyses have revealed that four cases of isolated PPAS in adulthood were homozygous for the ring finger protein 213 (RNF213) p.Arg4810Lys variant (also referred to as G to A alteration of rs112735431 and NM_001256071.3:c.14429G>A) [3]. RNF213 p.A...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Kanezawa, M., Shimokawahara, H., Tsuji, M., Suruga, K., Miyagi, A., Marunaka, M., Mukai, T., Kawaguchi, T., Yang, T.-Y., Yamaguchi, I., Nagasaki, M., Matsuda, F., Matsubara, H. Tags: Pulmonary vascular disease Research Letters Source Type: research

Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data
Conclusions Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Cividini, S., Sinha, I., Donegan, S., Maden, M., Rose, K., Fulton, O., Culeddu, G., Hughes, D. A., Turner, S., Tudur Smith, C., on behalf of the EINSTEIN Collaborative Group Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Adult-onset idiopathic peripheral pulmonary artery stenosis
Extract Peripheral pulmonary artery stenosis (PPS) is defined as the obstruction of the pulmonary artery from the pulmonary artery trunk to the peripheral arteries. PPS is considered a paediatric-onset disease associated with systemic congenital diseases (congenital rubella syndrome, Williams syndrome, Alagille syndrome, Ehlers–Danlos syndrome and Noonan syndrome) [1–4]. Apart from PPS associated with congenital syndromes, adult-onset idiopathic PPS has been reported [5]; however, it is rare and has not been reported in more than 10 cases. Transcatheter pulmonary angioplasty for chronic thromboembolic pulmonary...
Source: European Respiratory Journal - December 21, 2023 Category: Respiratory Medicine Authors: Tamura, Y., Tamura, Y., Shigeta, A., Hosokawa, K., Taniguchi, Y., Inami, T., Adachi, S., Tsujino, I., Nakanishi, N., Sato, K., Sakamoto, J., Tanabe, N., Takama, N., Nakamura, K., Kubota, K., Komura, N., Kato, S., Yamashita, J., Takei, M., Joho, S., Ishii, Tags: Pulmonary vascular disease Original Articles: Pulmonary vascular disease Source Type: research