Executive Summary Objectives Participants Evidence Validation Key Messages Introduction Rationale for a Change in the Approach to Classification of Idiopathic Interstitial Pneumonias Development of a New Classification of Idiopathic Interstitial Pneumonia Current Classification of IIP New ATS/ERS Classification Principles Guiding the Assessment of Patients with Idiopathic Interstitial Pneumonias The Diagnostic Process Is Dynamic Clinical Evaluation Radiological Evaluation Role of Surgical Lung Biopsy Unclassifiable Interstitial Pneumonia Bronchoalveolar Lavage Fluid Evaluation Idiopathic Pulmonary Fibrosis Clinical Features Radiologic Features Histologic Features IPF: Areas of Uncertainty Nonspecific Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features NSIP: Areas of Uncertainty Cryptogenic Organizing Pneumonia Clinical Features Radiologic Features Histologic Features COP: Areas of Uncertainty Acute Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features AIP: Areas of Uncertainty Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical Features Radiologic Features Histologic Features RB-ILD: Areas of Uncertainty Desquamative Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features DIP: Areas of Uncertainty Lymphoid Interstitial Pneumonia Clinical Features Radiologic Features Histologic Features LIP: Areas of Uncertainty References Appendix

American thoracic society/European respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias

### 1.1 An overview of the ILD guideline

Since the publication of the first BTS guidelines for diffuse lung disease nearly 10 years ago,1 the specialty has seen considerable change. The early discussions of the Guideline Group centred upon whether the revised document might consist of the 1999 document with minor adaptations. However, it was considered that too much change had taken place in the intervening years to justify a simple editorial approach. The last decade had seen the development of a new consensus terminology for the idiopathic interstitial pneumonias (IIP)2 stimulated, in part, by the identification of non-specific interstitial pneumonia (NSIP) as a discrete histological pattern with increasingly recognised clinical correlates.3 The better prognosis seen in fibrotic NSIP than in idiopathic pulmonary fibrosis (IPF)4 5 fuelled a more intense approach to diagnosis in cases of suspected IPF. This in turn has led to a radical change in accepted diagnostic gold standards, which have become increasingly multidisciplinary and dependent equally upon the skills of pathologists, radiologists and clinicians.6 NSIP, as a new entity, has posed particular difficulties. With more detailed studies of outcome specific to individual IIPs, especially IPF and fibrotic NSIP, the prognostic weighting given to pulmonary function impairment has been refined, especially with regard to longitudinal functional trends.7 Most important, with the standardisation of terminology, it became possible to recruit patients into multicentre treatment studies.8–10 With regard to IPF in particular, the last 3 years have seen more studies of treatment than in the previous history of the speciality, yet there is no universally accepted “best current treatment”.

### 1.2 Methodology for constructing guidelines and making recommendations

The overall process for generating BTS guidelines has been addressed in numerous recently published documents (available at http://www.brit-thoracic.org.uk/guidelines.html). The methodology applied herein is broadly similar and is not therefore described in detail. However, there are specific aspects in the …

https://thorax.bmj.com/content/thoraxjnl/63/Suppl_5/v1.full.pdf

Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society.

Organising pneumonia is defined histopathologically by intra-alveolar buds of granulation tissue, consisting of intermixed myofibroblasts and connective tissue. Although nonspecific, this histopathological pattern, together with characteristic clinical and imaging features, defines cryptogenic organising pneumonia when no cause or peculiar underlying context is found. Rapid clinical and imaging improvement is obtained with corticosteroid treatment, but relapses are common after stopping treatment.

https://erj.ersjournals.com/content/erj/28/2/422.full.pdf

Cryptogenic organising pneumonia

We present a typical case of Obliterant Bonchilitis with Organizative Pneumonia in a 73-years-old man. The diagnosis was established through minithoracotomy. Treated with high dosage of methylprednisolone, the clinical-radiological evolution was satisfactory. It is very important to know and correctly diagnose this entity, given its excellent therapeutical response.

Bronchiolitis obliterans with organizing pneumonia

Background 
Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited.


Objectives 
To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD.


Method 
Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features.


Results 
Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable.


Conclusions 
TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

/pdf/transbronchial-lung-cryobiopsy-in-the-diagnosis-of-fibrotic-29egyrdemg.pdf

Transbronchial Lung Cryobiopsy in the Diagnosis of Fibrotic Interstitial Lung Diseases

Bronchiolitis obliterans-organizing pneumonia: an Italian experience

In order to determine the diagnostic value of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) in cryptogenic organizing pneu- monia (COP) a prospective study was carried out. Thirty seven consecutive patients (20 males and 17 females) with clinicoradio- logical features of COP were enrolled in the study. The statistical analyses were completed in 35 cases. Twenty eight patients were diagnosed to have COP, all of them with a confirmatory biopsy. In seven cases, a different diagnosis was made. BAL cytological and phenotypical criteria considered for the diagnosis of COP were: a lymphocytosis of more than 25% (with a CD4/CD8 ratio less than 0.9); combined with at least two of the following data (foamy macrophages of >20%, and/or neutrophils of >5%, and/or eosinophils of >2% and <25%). TBLB speci- mens were classified as positive for COP if they showed: buds of granulation tis- sue within the centrilobular air spaces; infiltration of alveolar walls with chronic inflammatory cells; and preservation of alveolar architecture. BAL was performed in 34 patients; 17 cases were consistent with the final diag- nosis of COP (sensitivity 63%), and four cases were correctly classified as nega- tive (specificity 57%). BAL had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 29%. TBLB was performed in 32 patients; it correctly identified COP in 16 cases (sensitivity 64%), and six cases were correctly classified as negative (specificity 86%). TBLB had a PPV of 94% and a NPV of 40%. The accuracy of the examinations, that is the probability of correctly diag- nosing both diseased and nondiseased patients by BAL or TBLB, was 62 and 69%, respectively. Our findings suggest that the combination of cytological bronchoalveolar lavage and histological transbronchial lung biopsy data obtained during a fibreoptic pro- cedure appears to be an effective method for the initial investigation in crypto- genic organizing patients pneumonia presenting with patchy radiographic shadows.

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic

In order to determine the diagnostic value of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) in cryptogenic organizing pneumonia (COP) a prospective study was carried out. Thirty seven consecutive patients (20 males and 17 females) with clinicoradiological features of COP were enrolled in the study. The statistical analyses were completed in 35 cases. Twenty eight patients were diagnosed to have COP, all of them with a confirmatory biopsy. In seven cases, a different diagnosis was made. BAL cytological and phenotypical criteria considered for the diagnosis of COP were: a lymphocytosis of more than 25% (with a CD4/CD8 ratio less than 0.9); combined with at least two of the following data (foamy macrophages of > 20%, and/or neutrophils of > 5%, and/or eosinophils of > 2% and < 25%). TBLB specimens were classified as positive for COP if they showed: buds of granulation tissue within the centrilobular air spaces; infiltration of alveolar walls with chronic inflammatory cells; and preservation of alveolar architecture. BAL was performed in 34 patients; 17 cases were consistent with the final diagnosis of COP (sensitivity 63%), and four cases were correctly classified as negative (specificity 57%). BAL had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 29%. TBLB was performed in 32 patients; it correctly identified COP in 16 cases (sensitivity 64%), and six cases were correctly classified as negative (specificity 86%). TBLB had a PPV of 94% and a NPV of 40%. The accuracy of the examinations, that is the probability of correctly diagnosing both diseased and nondiseased patients by BAL or TBLB, was 62 and 69%, respectively. Our findings suggest that the combination of cytological bronchoalveolar lavage and histological transbronchial lung biopsy data obtained during a fibreoptic procedure appears to be an effective method for the initial investigation in cryptogenic organizing patients pneumonia presenting with patchy radiographic shadows.

https://erj.ersjournals.com/content/erj/9/12/2513.full.pdf

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic organizing pneumonia

In order to assess the diagnostic yield of bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) in pulmonary diseases with a ground-glass and/or alveolar pattern on high-resolution computed tomography (HRCT) scan, a prospective study was undertaken. Thirty-six patients (17 males, 19 females), mean age 53 yrs, selected on the basis of the presence of an alveolar and/or ground-glass pattern on chest HRCT scan, were submitted to fibreoptic bronchoscopy. All patients underwent BAL. TBBs were performed in 33 cases. A specific diagnosis was achieved, taking into account data obtained by means of serology, microbiology, cytology and histopathology in appropriate clinical settings. Twelve (33%) patients only had the appearance of a ground-glass opacity, whereas 24 (67%) had associated areas of airspace consolidation. BAL was performed in all cases and gave a definitive diagnosis in 21 (58%). The diagnostic yield of BAL in patients with only ground-glass opacities was no different from that in those patients also showing areas of alveolar consolidation (58 versus 58%). In eight patients (six with ground-glass opacity and two with alveolar consolidation), BAL provided useful but not definitive information. In these patients, a definitive diagnosis was achieved by means of TBB in seven cases and by open lung biopsy in one case. TBB was performed in 33 out of 36 patients and gave positive results in 25 (76%). The diagnostic yield of TBB in patients showing areas of alveolar consolidation was significantly higher than in those with pure ground-glass opacity, i.e. 95% (21 of 22) and 36% (4 of 11) respectively (p < 0.001). BAL and TBB were performed during the same bronchoscopy in 33 patients, and an accurate diagnosis was achieved in 30 (91%). Overall, the diagnostic yield of TBB (76%) and BAL (56%) did not differ significantly in the whole patient group (p = 0.12), or in patients with a ground-glass opacification (58 versus 36%, p = 0.3). However, in patients with areas of alveolar consolidation, the diagnostic sensitivity of TBB (95%) was significantly greater than the diagnostic sensitivity of BAL (54%) (p = 0.03). In conclusion this study shows that high-resolution computed tomography can be helpful in predicting the diagnostic accuracy of bronchological procedures, in particular of bronchoalveolar lavage and transbronchial biopsy, and that alveolar and/or ground-glass are favourable patterns for these diagnostic tools.

Bronchoalveolar lavage and transbronchial lung biopsy in alveolar and/or ground-glass opacification.

The Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a fatal and immune-mediated idiosyncratic drug reaction, with symptoms of fever, skin eruptions (that involves more than half of the body surface), facial oedema and hematological disorders, all presenting within the latent period following drug intake. Effects can also be seen on multiple organs, most notably hepatitis in liver and acute interstitial nephritis in kidney, generally post-administration of allopurinol. The European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) classifies the DRESS Syndrome cases as "definite", "probable" or "possible", based on clinical and laboratory features. Different pathogenetic mechanisms have been involved in this disease, including immunological reactions and HHV-6 reactivation. In our experience, a 72-year-old male, affected by myeloma in peritoneal dialysis, developed a rare case of DRESS syndrome after lenalidomide administration (less than ten cases are known) with HHV-6 reactivation. According to literature, we withdrew the drug and gave methylprednisolone 0,8 mg/kg orally and IVIG 1 gr/kg for two days. Despite this therapy, DRESS syndrome relapsed during steroid taper with rash, thrombocytopenia, hepatitis and high troponin level. A single cycle of intravenous immunoglobulin 0,5 g/kg for four days was enough for syndrome remission. Only few cases are reported in literature, but because of the increasing use of lenalidomide and the autoimmune sequelae of DRESS syndrome, a broad workup and a multidisciplinar careful approach could help in diagnosis, treatment and follow-up.

S. Cazzato

Papers

Bronchiolitis obliterans-organizing pneumonia: an Italian experience

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic

The diagnostic value of bronchoalveolar lavage and transbronchial lung biopsy in cryptogenic organizing pneumonia

Bronchoalveolar lavage and transbronchial lung biopsy in alveolar and/or ground-glass opacification.

Skin reaction with Eosinophilia and Systemic Symptoms after lenalidomide in peritoneal Dialysis.