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Different clinical settings characterized by diffuse alveolar damage (DAD) pathology. This non-proportional figure denotes the incoherence of the clinical significance of acute respiratory distress syndrome (ARDS), acute interstitial pneumonia (AIP), and idiopathic pulmonary fibrosis (IPF) exacerbations in which DAD, despite being the common denominator, develops upon different histology substrates (UIP in IPF exacerbations, normal lungs in AIP, and normal or diseased lungs in ARDS) and, according to current definitions, presents at different time intervals: 7 days for ARDS, 4 weeks for IPF exacerbations, and 2 months for AIP. This incoherence led also to a different pharmacologic approach, which proved to be unsuccessful at least in AIP and in IPF true exacerbations. ALI, acute lung injury.
Source publication
Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course. IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause...
Context in source publication
Context 1
... further considerations have to be made. ALI/ARDS, acute interstitial pneumonia (AIP), and IPF exacerbations have common clinical, physiological, imaging, and histopathology features, and it is incon ceiv- able that they do not also have common etiopathogenetic mechanisms ( Figure 5). ALI/ARDS develops by diff erent insults to the lung, and the mainstay of its treatment is provision of excellent supportive care and etiologic manage ment of the underlying cause [46]. ...Similar publications
Background/aims:
Diffuse alveolar damage (DAD) is the histopathologic hallmark of acute respiratory distress syndrome (ARDS). However, there are several non-DAD conditions mimicking ARDS. The purpose of this study was to investigate the histopathologic heterogeneity of ARDS revealed by surgical lung biopsy and its clinical relevance.
Methods:
We...
Background
Although diffuse alveolar damage (DAD) is considered the typical histological pattern of acute respiratory distress syndrome (ARDS), only half of patients exhibit this morphological hallmark. Patients with DAD may have higher mortality than those without DAD. Therefore, we aimed to identify the factors associated with DAD in patients wit...
Acute respiratory distress syndrome (ARDS) describes the clinical syndrome associated with the morphologic lesion termed diffuse alveolar damage (DAD). At presentation, (early) ARDS manifests with acute and diffuse injury to the endothelial and epithelial lining of the terminal respiratory units and causes increased vascular permeability with prote...
Acute respiratory distress syndrome (ARDS) describes the clinical syndrome associated with the morphologic lesion termed diffuse alveolar damage (DAD). At presentation, early ARDS manifests with acute and diffuse injury to the endothelial and epithelial linings of the terminal respiratory units and causes increased vascular permeability with protei...
Citations
... However, the aforementioned considerations regarding theory and practice of IPF-AEs were not universally adopted, and our group of investigators in a review article based on own clinical observation sustained that in the clinical context of a rapidly deteriorating IPF patient, clinicians are faced with three different scenarios: first, the progression toward the "final end" of the disease where spontaneous breathing becomes unsupportable because of the excessive fibrotic lung derangement and where palliation of breathlessness appears the only option; second, the development of a new clinical complication (infection, embolism, or heart decompensation), reversible when promptly diagnosed and appropriately treated; and third, the true development of ARDS upon IPF (Papiris et al., 2010). In this clinical context and since in the etiology of ARDS, pneumonia and sepsis are the most commonly encountered triggering factors, and in those years, most patients were receiving immunosuppressants that clearly predisposed them to infections; the authors suggested the withdrawal of the aforementioned immunosuppressants and treatment according to the ARDS guidelines: provision of excellent supportive care, any effort to identify and treat triggering factors, and in the process of identification or if unidentified, administration of antibiotics according to the immunological status and clinical context of the patient (Ranieri et al., 2012). ...
... This is especially true in high-risk conditions associated with ILDs such as neutropenia, immune-suppressive treatment, and onco-hematologic diseases [1,2,28]. In fact, BAL is likely to discriminate between infective exacerbations and "acceleration" of IPF or other ILDs [10,[29][30][31]; thus this may be of help for the physician to solve out the ethical dilemma correlated to the choice of withholding ventilator support in subjects developing severe ARF or withdrawing mechanical ventilation in terminally ill ventilator dependent patients. ...
Bronchoscopy may be considered the “added value” in the diagnostic and therapeutic pathway of different clinical scenarios occurring in acute respiratory critically ill patients. Rigid bronchoscopy is mainly employed in emergent clinical situations due to central airways obstruction, haemoptysis, and inhaled foreign body. Flexible bronchoscopy (FBO) has larger fields of acute applications. In intensive care settings, FBO is useful to facilitate intubation in difficult airways, guide percutaneous dilatational tracheostomy, and mucous plugs causing lobar/lung atelectasis. FBO plays a central diagnostic role in acute respiratory failure caused by intra-thoracic tumors, interstitial lung diseases, and suspected severe pneumonia. “Bronchoscopic” sampling has to be considered when “non-invasive” techniques are not diagnostic in suspected ventilator-associated pneumonia and in non-ventilated immunosuppressed patients. The combined use of either noninvasive ventilation (NIV) or High-flow nasal cannula (HFNC) with bronchoscopy is useful in different scenarios; the largest body of proven successful evidence has been found for NIV-supported diagnostic FBO in non-ventilated high risk patients to prevent and avoid intubation. The expected diagnostic/therapeutic goals of acute bronchoscopy should be balanced against the potential severe risks (i.e., cardio-pulmonary complications, bleeding, and pneumothorax). Expertise of the team is fundamental to achieve the best rate of success with the lowest rate of complications of diagnostic and therapeutic bronchoscopic procedures in acute clinical circumstances.
... During its course, many patients develop a sudden acute respiratory deterioration, of unknown cause, associated with high mortality. This event is referred as acute exacerbation of IPF (AE-IPF) and is characterized by the development of diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP) [2,3]. Even though diverse trigger factors have been proposed to contribute to the appearance of these catastrophic events, the exact etiology of the majority of the cases remains unknown [2,3]. ...
... This event is referred as acute exacerbation of IPF (AE-IPF) and is characterized by the development of diffuse alveolar damage (DAD) upon usual interstitial pneumonia (UIP) [2,3]. Even though diverse trigger factors have been proposed to contribute to the appearance of these catastrophic events, the exact etiology of the majority of the cases remains unknown [2,3]. ...
Background
Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL).
Methods
All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O 3 , NO 2 , PM 2.5 [and PM 10 , based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants’ levels with AE-IPF and inflammatory mediators adjusting for potential confounders.
Results
118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 μg/m ³ increase in previous-year mean level of NO 2 (OR = 1.52, 95%CI:1.15–2.0, p = 0.003), PM 2.5 (OR = 2.21, 95%CI:1.16–4.20, p = 0.016) and PM 10 (OR = 2.18, 95%CI:1.15–4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O 3 was positively associated with %change of IL-4 ( p = 0.014) whilst PM 2.5 , PM 10 and NO 2 were inversely associated with %changes of IL-4 ( p = 0.003, p = 0.003, p = 0.032) and osteopontin ( p = 0.013, p = 0.013, p = 0.085) respectively.
Conclusions
Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.
... IPF presents with an ominous prognosis with a median survival of around five years [1]. The development of an acute exacerbation (AE), histologically diffuse alveolar damage (DAD) upon UIP, represents the most devastating of its complications and leads to death the majority of patients admitted to intensive care unit (ICU) [2,3,4]. Viral infections in the setting of an altered host lung microbiome are likely important triggers of IPF-AE's and subsequent ARDS [4,5]. ...
... İPF-AA tedavisi ile ilgili Fransız rehberinde ise kortikosteroid ve destek tedavi dışında intravenöz siklofosfamid tedavisi, tromboemboli şüphesi olanlarda antikoagülan tedavi, enfeksiyonun dışlanamadığı olgularda ise geniş spektrumlu antibiyotiklerin de uygulanabileceği belirtilmektedir (60) . Olası infektif bir etken tanımlanamayan hastalarda daha önceki kültür sonuçları, mekanik ventilatör destek başlangıcı ve sonuçları gibi faktörleri dikkate alan ampirik antimikrobiyal tedavi verilmelidir (61) . ...
... azaltarak hasta konforunu artıran önemli bir palyatif tedavi seçeneğidir (61)(62)(63) . Yapılan bir çalışmada, 2007-2015 tarihleri arasında İPF-AA tanısı almış ve mekanik ventilasyon desteği verilen 62 hastanın retrospektif olarak değerlendirilmiş, pozitif ekspiryum sonu basınç (PEEP) uygulanan hastaların daha iyi sağkalım gösterdiği saptanmıştır (64) . ...
... Although recent data suggest a reduction in mortality risk [8], the five-year survival rate remains extremely low with a median survival after diagnosis of only 3-5 years [8,9]. Treatment with corticosteroids and immunosuppressants has proven to be ineffective in the stabilization of pulmonary function and improvement of survival [10]. Recently, however, a better management of the disease has been achieved with pirfenidone (PFD, 5-methyl-1-phenyl-2-(1H)-pyridone), a drug originally approved for the specific treatment of mild to moderate IPF [8]. ...
... Acute-phase ARDS-associated alveolar collapse and inflammation leads to pulmonary volume reduction[2]. The chronic phase of ARDS may be 4 characterized by pulmonary fibroproliferation, which also leads to diminished lung compliance [3]. The patient was trained to undertake spontaneous deep breathing to maintain lung recruitment. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mostly presents with mild respiratory symptoms, although more severely affected patients may die of refractory acute respiratory distress syndrome (ARDS). The pulmonary function of surviving patients may decrease significantly in the early stages post-weaning due to the massive alveolar damage. Therefore, early pulmonary rehabilitation is important in these patients. We would like to share our experience of early pulmonary rehabilitation program in severe SARS-CoV-2 pneumonia, and hope that can remind ICUs of pulmonary rehabilitation in managing severe SARS-CoV-2 pneumonia.
... In a retrospective study of patients with IPF, Vianello et al. showed that outcomes were quite poor among those receiving NIV for acute respiratory failure, but that its use prevented the need for intubation and reduced the complications and death rates in selected patients20 . NIV has also been used sporadically as a life-sustaining measure after acute respiratory failure to mitigate against the high mortality among patients awaiting lung transplantation21 . The 'Palliation Use of NIV' Task Force from the Society of Critical Care Medicine 22 suggested classifying NIV use into three categories for patients with acute respiratory failure, as shown in Figure 2. ...
... MDS was classified as refractory anemia (RA) and RA with ring sideroblasts (RARS) in two patients both presenting low values for the international prognosis system score (IPSS Based on this case-series four out of five patients with the co-existence of IPF and MDS developed an IPF acute exacerbation that was not reversible. An extensive workup was performed to exclude obvious causes of the deterioration such as infection, aspiration or drug toxicity [12]. Although azacytidine has been used safely in elderly patients and has been shown to significantly improve survival and quality of life [13], our observations suggest that this drug may not be as effective in patients with both IPF and MDS. ...
... Azacytidine is a hypomethylating agent and re-expression of tumor-suppressor genes has been suggested as a possible mechanism of action. However, hypomethylating activity is global and Azacytidine has a pleotropic effect on the immune system and could trigger the development of diffuse alveolar damage upon usual interstitial pneumonia through either an eventual toxicity of the drug to the lungs [1,13] or infection because of the increased immunosuppression upon the vulnerable lungs of IPF patients [12,[14][15][16]. ...
Abstract Previous studies have shown that the co-existence of bone marrow failure and pulmonary fibrosis in a single patient or in a family is suggestive of telomere related genes (TRG) germline mutations. This study presents the genetic background, clinical characteristics, and outcome of a group of five Greek patients co-affected with IPF and MDS. Four out of five patients developed an IPF acute exacerbation that was not reversible. We failed to detect any mutation in the TERT, TERC, DKC1, TINF2, RTEL1, PARN, NAF1, ACD, NHP2 and NOP10 genes in any patient. Moreover, telomere length was normal in the two patients tested. This could suggest that although the co-occurence of IPF and MDS are suggestive of TRG mutation in patients
... Infection may also play a role in disease progression in patients with IPF, in whom active infection carries a high morbidity and mortality, [9] whereas immunosuppression (e.g., combination prednisone, azathioprine and N-acetylcysteine) increases the risk of death and hospitalizations [10]. Notably, the utility of corticosteroids in IPF, particularly in the acute phase of the disease, had been questioned well before the PANTHER trial [11][12][13]. ...
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease that commonly affects older adults and is associated with the histopathological and/or radiological patterns of usual interstitial pneumonia (UIP). Despite significant advances in our understanding of disease pathobiology and natural history, what causes IPF remains unknown. A potential role for infection in the disease’s pathogenesis and progression or as a trigger of acute exacerbation has long been postulated, but initial studies based on traditional culture methods have yielded inconsistent results. The recent application to IPF of culture-independent techniques for microbiological analysis has revealed previously unappreciated alterations of the lung microbiome, as well as an increased bacterial burden in the bronchoalveolar lavage (BAL) of IPF patients, although correlation does not necessarily entail causation. In addition, the lung microbiome remains only partially characterized and further research should investigate organisms other than bacteria and viruses, including fungi. The clarification of the role of the microbiome in the pathogenesis and progression of IPF may potentially allow its manipulation, providing an opportunity for targeted therapeutic intervention.
