Chronic respiratory diseases, including pulmonary fibrosis, chronic obstructive pulmonary disease (COPD) and lung cancer, are the second leading cause of death among Europeans. Despite this, there have been only a few therapeutic advances in these conditions over the past 20 years. In this review we provide evidence that targeting the epidermal growth factor receptor (EGFR) signalling pathway may represent a novel therapeutic panacea for treating chronic lung disease. Using evidence from human patient samples, transgenic animal models, and cell and molecular biology studies we highlight the roles of this signalling pathway in lung development, homeostasis, repair, and disease ontogeny. We identify mechanisms underlying lung EGFR pathway regulation and suggest how targeting these mechanisms using new and existing therapies has the potential to improve future lung cancer, COPD and pulmonary fibrosis patient outcomes. @ERSpublications Deregulated EGFR pathway signalling is a common event and an important therapeutic target for many chronic lung diseases

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Accidental foreign body aspiration is more common in children than in adults. It is one of the most common causes of accidental death in young children. Retrieval of the foreign body by rigid or flexible bronchoscopy is successful in the majority of cases. We describe a case of a 14-year-old girl who inhaled a scarf pin. Flexible bronchoscopy was partly successful and managed to bring the pin up from a segmental bronchus into the left lower lobe bronchus and then into the throat. Unfortunately, it was reaspirated by the patient into the lower trachea. A rigid bronchoscopy under general anesthesia was planned; however, the patient managed to cough the foreign body out spontaneously, thus avoiding further interventions.

BACKGROUNDHepatic hydrothorax is a complication commonly seen in up to 10% of patients with advanced liver disease. 1 The management of hepatic hydrothorax poses great diffi culties to physicians with current treatment options limited.We present a case where an intrapleural catheter (IPC) was successfully used in the management of a hepatic hydrothorax, improving quality of life and allowing medical management to take effect. There are very few reports of the use of IPC for this indication and we feel others would benefi t from consideration of this therapy. CASE PRESENTATIONA 52-year-old Caucasian female, with a background of systemic lupus erythematosus, hypothyroidism and splenic lymphoma (managed by splenectomy in 2006), presented with multiple episodes of shortness of breath over a period of 5 months. She was a life-long smoker, with minimal alcohol consumption and no signifi cant family history to note. The patient lives at home with her husband, daughter and newly born grand daughter. Frequent hospital admissions imposed additional social diffi culties upon the family.Novel treatment (new drug/intervention; established drug/procedure in new situation)

Respiratory cytology continues to play a central role in the diagnosis and staging of thoracic malignancy, although over time indications have changed. Historically, sputum cytology and endobronchial brushings and washings figured prominently, but with the advent of endobronchial and endoscopic ultrasound much greater emphasis is placed on fine needle aspirates from lymph nodes. The advent of targeted sequencing panels for genomic profiling to identify driver mutations and PD‐L1 directed immunotherapy means that there is a need to extract increasing amounts of diagnostic and predictive information from ever smaller amounts of diagnostic material. Recent work has demonstrated that cytology samples are well suited to delivering the information required, but in order to understand the limitations of clinical and laboratory techniques, a close working relationship between pathologist and thoracic oncologist is needed to optimise sample procurement and utilisation.

Lung cancer is the biggest cancer killer in the UK and despite recent therapeutic advances there is a desperate need for new therapies to improve outcomes from this devastating disease. Through defining the spatial location of the airway epithelial stem or progenitor cell populations and their mechanisms of maintenance and repair of the epithelium it is becoming clear that these populations are situated at areas corresponding to those involved in lung cancer initiation. We explore the evidence for stem cells being the cancer initiator cell and for a 'lung cancer stem cell' within tumours that may be the cause of resistance to current therapies.

Lung squamous cell carcinoma (LUSC) accounts for a significant proportion of cancer deaths worldwide, and is preceded by the appearance of progressively disorganised pre-invasive lesions in the airway epithelium. Yet the biological mechanisms underlying progression of pre-invasive lesions into invasive LUSC are not fully understood. LRIG1 is downregulated in pre-invasive airway lesions and invasive LUSC tumours and this correlates with decreased lung cancer patient survival.Using an Lrig1 knock-in reporter mouse and human airway epithelial cells collected at bronchoscopy, we show that during homeostasis LRIG1 is heterogeneously expressed in the airway epithelium. In basal airway epithelial cells, the suspected cell of origin of LUSC, LRIG1 identifies a subpopulation of progenitor cells with higher in vitro proliferative and self-renewal potential in both the mouse and human. Using the N-nitroso-tris-chloroethylurea (NTCU)-induced murine model of LUSC, we find that Lrig1 loss-of-function leads to abnormally high cell proliferation during the earliest stages of pre-invasive disease and to the formation of significantly larger invasive tumours, suggesting accelerated disease progression.Together, our findings identify LRIG1 as a marker of basal airway progenitor cells with high proliferative potential and as a regulator of pre-invasive lung cancer progression. This work highlights the clinical relevance of LRIG1 and the potential of the NTCU-induced LUSC model for functional assessment of candidate tumour suppressors and oncogenes.

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